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Sample records for pharmacogenetics research network

  1. The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Overcoming Challenges of Real-World Implementation

    PubMed Central

    Shuldiner, AR; Relling, MV; Peterson, JF; Hicks, JK; Freimuth, RR; Sadee, W; Pereira, NL; Roden, DM; Johnson, JA; Klein, TE

    2013-01-01

    The pace of discovery of potentially actionable pharmacogenetic variants has increased dramatically in recent years. However, the implementation of this new knowledge for individualized patient care has been slow. The Pharmacogenomics Research Network (PGRN) Translational Pharmacogenetics Program seeks to identify barriers and develop real-world solutions to implementation of evidence-based pharmacogenetic tests in diverse health-care settings. Dissemination of the resulting toolbox of “implementation best practices” will prove useful to a broad audience. PMID:23588301

  2. The Pharmacogenetics Research Network: From SNP Discovery to Clinical Drug Response

    PubMed Central

    Giacomini, KM; Brett, CM; Altman, RB; Benowitz, NL; Dolan, ME; Flockhart, DA; Johnson, JA; Hayes, DF; Klein, T; Krauss, RM; Kroetz, DL; McLeod, HL; Nguyen, AT; Ratain, MJ; Relling, MV; Reus, V; Roden, DM; Schaefer, CA; Shuldiner, AR; Skaar, T; Tantisira, K; Tyndale, RF; Wang, L; Weinshilboum, RM; Weiss, ST; Zineh, I

    2016-01-01

    The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism. PMID:17339863

  3. Methods for analysis in pharmacogenomics: lessons from the Pharmacogenetics Research Network Analysis Group.

    PubMed

    Srinivasan, Balaji S; Chen, Jinbo; Cheng, Cheng; Conti, David; Duan, Shiwei; Fridley, Brooke L; Gu, Xiangjun; Haines, Jonathan L; Jorgenson, Eric; Kraja, Aldi; Lasky-Su, Jessica; Li, Lang; Rodin, Andrei; Wang, Dai; Province, Mike; Ritchie, Marylyn D

    2009-02-01

    Each year, the Pharmacogenetics Research Network (PGRN) holds an analysis workshop for the members of the PGRN to share new methodologies, study design approaches and to discuss real data applications. This event is closed to members of the PGRN, but the methods presented are relevant to others conducting pharmacogenomics research. This special report describes many of the novel approaches discussed at the workshop and provides a resource for investigators in the field performing pharmacogenomics data analysis. While the focus is pharmacogenomics, the methods discussed are far ranging and have relevance to all types of genetic association studies: identifying noncoding variants and tag-SNPs, haplotype analysis, multivariate techniques, quantitative trait analysis, gene-gene and gene-environment interactions, and genome-wide association studies. The goal is to introduce readers to the topics discussed at the workshop and provide a direction for future development of analysis tools and methods for analysis of pharmacogenomic data.

  4. Priorities and standards in pharmacogenetic research.

    PubMed

    Need, Anna C; Motulsky, Arno G; Goldstein, David B

    2005-07-01

    The current enthusiasm for pharmacogenetics draws much of its inspiration from the relatively few examples of polymorphisms that have marked and seemingly clinically relevant effects on drug response. In this regard, pharmacogenetic research has paralleled the study of human disease, which has enjoyed success in identifying mutations underlying mendelian conditions. Progress in deciphering the genetics of complex diseases, involving the interaction of multiple genes with each other and with the environment has been considerably less successful. In most instances, drug responses will probably also prove to be complex, influenced by both the environment and multiple genetic factors. For pharmacogenetics to deliver on its potential, this complexity will need to be recognized and accommodated, both in basic research and in clinical application of pharmacogenetics. As the attention of researchers begins to shift toward more systematic pharmacogenetic investigations, we suggest some priorities and standards for pharmacogenetic research.

  5. Genome-wide association studies in pharmacogenetics research debate

    PubMed Central

    Bailey, Kent R; Cheng, Cheng

    2016-01-01

    Will genome-wide association studies (GWAS) ‘work’ for pharmacogenetics research? This question was the topic of a staged debate, with pro and con sides, aimed to bring out the strengths and weaknesses of GWAS for pharmacogenetics studies. After a full day of seminars at the Fifth Statistical Analysis Workshop of the Pharmacogenetics Research Network, the lively debate was held – appropriately – at Goonies Comedy Club in Rochester (MN, USA). The pro side emphasized that the many GWAS successes for identifying genetic variants associated with disease risk show that it works; that the current genotyping platforms are efficient, with good imputation methods to fill in missing data; that its global assessment is always a success even if no significant associations are detected; and that genetic effects are likely to be large because humans have not evolved in a drug-therapy environment. By contrast, the con side emphasized that we have limited knowledge of the complexity of the genome; limited clinical phenotypes compromise studies; the likely multifactorial nature of drug response clouding the small genetic effects; and limitations of sample size and replication studies in pharmacogenetic studies. Lively and insightful discussions emphasized further research efforts that might benefit GWAS in pharmacogenetics. PMID:20235786

  6. Ethical perspectives on translational pharmacogenetic research involving children.

    PubMed

    Madadi, Parvaz

    2015-02-01

    Children represent a special population characterized by dynamic changes which may affect drug safety and efficacy. The interplay of pharmacogenetics with physiological alterations that occur throughout development is an area of increasing research focus. Given the translational nature of pharmacogenetic research, it is possible that pharmacogenetic research results may possess clinically actionable information. The potential long-term implications of pharmacogenetic test results throughout the lifespan of the child, and the potential impact of the results for other members of the family need to be considered. Comprehensive counselling and communication strategies may need to be integrated as part of pharmacogenetic research studies in children. PMID:25504355

  7. Consent in psychiatric biobanks for pharmacogenetic research.

    PubMed

    van der Baan, Frederieke H; Bernabe, Rose D C; Bredenoord, Annelien L; Gregoor, Jochem G; Meynen, Gerben; Knol, Mirjam J; van Thiel, Ghislaine J M W

    2013-04-01

    In psychiatric practice, pharmacogenetics has the potential to identify patients with an increased risk of unsatisfactory drug responses. Genotype-guided treatment adjustments may increase benefits and reduce harm in these patients; however, pharmacogenetic testing is not (yet) common practice and more pharmacogenetic research in psychiatric patients is warranted. An important precondition for this type of research is the establishment of biobanks. In this paper, we argue that, for the storage of samples in psychiatric biobanks, waiving of consent is not ethically justifiable since the risks cannot be considered minimal and the argument of impracticability does not apply. An opt-out consent procedure is also not justifiable, since it presumes competence while the decisional competence of psychiatric patients needs to be carefully evaluated. We state that an enhanced opt-in consent procedure is ethically necessary, i.e. a procedure that supports the patients' decision-making at the time when the patient is most competent. Nevertheless, such a procedure is not the traditional exhaustive informed consent procedure, since this is not feasible in the case of biobanking. PMID:22607776

  8. Application of routine electronic health record databases for pharmacogenetic research.

    PubMed

    Yasmina, A; Deneer, V H M; Maitland-van der Zee, A H; van Staa, T P; de Boer, A; Klungel, O H

    2014-06-01

    Inter-individual variability in drug responses is a common problem in pharmacotherapy. Several factors (non-genetic and genetic) influence drug responses in patients. When aiming to obtain an optimal benefit-risk ratio of medicines and with the emergence of genotyping technology, pharmacogenetic studies are important for providing recommendations on drug treatments. Advances in electronic healthcare information systems can contribute to increasing the quality and efficiency of such studies. This review describes the definition of pharmacogenetics, gene selection and study design for pharmacogenetic research. It also summarizes the potential of linking pharmacoepidemiology and pharmacogenetics (along with its strengths and limitations) and provides examples of pharmacogenetic studies utilizing electronic health record databases. PMID:24581153

  9. Potential of adaptive clinical trial designs in pharmacogenetic research.

    PubMed

    van der Baan, Frederieke H; Knol, Mirjam J; Klungel, Olaf H; Egberts, Antoine Cg; Grobbee, Diederick E; Roes, Kit C B

    2012-04-01

    Adaptive trial designs can be beneficial in pharmacogenetic research when prior uncertainty exists regarding the exact role and clinical relevance of genetic variability in drug response. This type of design enables us to learn about the effect of the genetic variability on drug response and to immediately use this information for the remainder of the study. For different types of adaptive trial designs, we discuss when and how the designs are suitable for pharmacogenetic research: adaptation of randomization, adaptation of patient enrollment and adaptive enrichment. To illustrate the potential benefits of an adaptive design over a fixed design, we simulated an adaptive trial based on the results of the IPASS trial. With a simple model we show that for this example an adaptive enrichment design would have led to a smaller trial, with less EGF receptor mutation-negative patients unnecessarily exposed to the drug, without compromising the α level or reducing power. PMID:22462749

  10. Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls

    PubMed Central

    Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Kumar Bhattacharjee, Abesh; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

    2013-01-01

    The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment. PMID:23793356

  11. Pharmacogenetic research in partnership with American Indian and Alaska Native communities.

    PubMed

    Woodahl, Erica L; Lesko, Lawrence J; Hopkins, Scarlett; Robinson, Renee F; Thummel, Kenneth E; Burke, Wylie

    2014-06-01

    Pharmacogenetics is a subset of personalized medicine that applies knowledge about genetic variation in gene-drug pairs to help guide optimal dosing. There is a lack of data, however, about pharmacogenetic variation in underserved populations. One strategy for increasing participation of underserved populations in pharmacogenetic research is to include communities in the research process. We have established academic-community partnerships with American Indian and Alaska Native people living in Alaska and Montana to study pharmacogenetics. Key features of the partnership include community oversight of the project, research objectives that address community health priorities, and bidirectional learning that builds capacity in both the community and the research team. Engaging the community as coresearchers can help build trust to advance pharmacogenetic research objectives.

  12. Pharmacogenetic research in partnership with American Indian and Alaska Native communities

    PubMed Central

    Woodahl, Erica L; Lesko, Lawrence J; Hopkins, Scarlett; Robinson, Renee F; Thummel, Kenneth E; Burke, Wylie

    2014-01-01

    Pharmacogenetics is a subset of personalized medicine that applies knowledge about genetic variation in gene–drug pairs to help guide optimal dosing. There is a lack of data, however, about pharmacogenetic variation in underserved populations. One strategy for increasing participation of underserved populations in pharmacogenetic research is to include communities in the research process. We have established academic–community partnerships with American Indian and Alaska Native people living in Alaska and Montana to study pharmacogenetics. Key features of the partnership include community oversight of the project, research objectives that address community health priorities, and bidirectional learning that builds capacity in both the community and the research team. Engaging the community as coresearchers can help build trust to advance pharmacogenetic research objectives. PMID:25141898

  13. Pharmacogenetic research in partnership with American Indian and Alaska Native communities.

    PubMed

    Woodahl, Erica L; Lesko, Lawrence J; Hopkins, Scarlett; Robinson, Renee F; Thummel, Kenneth E; Burke, Wylie

    2014-06-01

    Pharmacogenetics is a subset of personalized medicine that applies knowledge about genetic variation in gene-drug pairs to help guide optimal dosing. There is a lack of data, however, about pharmacogenetic variation in underserved populations. One strategy for increasing participation of underserved populations in pharmacogenetic research is to include communities in the research process. We have established academic-community partnerships with American Indian and Alaska Native people living in Alaska and Montana to study pharmacogenetics. Key features of the partnership include community oversight of the project, research objectives that address community health priorities, and bidirectional learning that builds capacity in both the community and the research team. Engaging the community as coresearchers can help build trust to advance pharmacogenetic research objectives. PMID:25141898

  14. Ethical issues in developing pharmacogenetic research partnerships with American Indigenous communities.

    PubMed

    Boyer, B B; Dillard, D; Woodahl, E L; Whitener, R; Thummel, K E; Burke, W

    2011-03-01

    Pharmacogenetic research offers the potential to improve the safety and efficacy of drug prescribing. Assuring that the benefits of this research reach indigenous and other medically underserved people is an important justice concern. First, however, a legacy of mistrust, derived from traditional research practices that disempower communities, must be overcome. Linking pharmacogenetic research to collaborative, power-sharing research partnerships provides a valuable opportunity to develop new and positive precedents for genetic research in indigenous communities. PMID:21326261

  15. Partnership with the Confederated Salish and Kootenai Tribes: Establishing an Advisory Committee for Pharmacogenetic Research

    PubMed Central

    Morales, Chelsea T.; Muzquiz, LeeAnna I.; Howlett, Kevin; Azure, Bernie; Bodnar, Brenda; Finley, Vernon; Incashola, Tony; Mathias, Cheryl; Laukes, Cindi; Beatty, Patrick; Burke, Wylie; Pershouse, Mark A.; Putnam, Elizabeth A.; Trinidad, Susan Brown; James, Rosalina; Woodahl, Erica L.

    2016-01-01

    Background Inclusion of American Indian and Alaska Native (AI/AN) populations in pharmacogenetic research is key if the benefits of pharmacogenetic testing are to reach these communities. Community-based participatory research (CBPR) offers a model to engage these communities in pharmacogenetics. Objectives An academic-community partnership between the University of Montana and the Confederated Salish and Kootenai Tribes (CSKT) was established to engage the community as partners and advisors in pharmacogenetic research. Methods A community advisory committee, the Community Pharmacogenetics Advisory Council (CPAC), was established to ensure community involvement in the research process. To promote bidirectional learning, researchers gave workshops and presentations about pharmacogenetic research to increase research capacity and CPAC members trained researchers in cultural competencies. As part of our commitment to a sustainable relationship, we conducted a self-assessment of the partnership, which included surveys and interviews with CPAC members and researchers. Results Academic and community participants agree that the partnership has promoted a bidirectional exchange of knowledge. Interviews showed positive feedback from the perspectives of both the CPAC and researchers. CPAC members discussed their trust in and support of the partnership as well as having learned more about research processes and pharmacogenetics. Researchers discussed their appreciation of CPAC involvement in the project and guidance the group provided in understanding the CSKT community and culture. Discussion We have created an academic-community partnership to ensure CSKT community input and to share decision-making about pharmacogenetic research. Our CBPR approach may be a model for engaging AI/AN people, and other underserved populations, in genetic research. PMID:27346763

  16. Communicating pharmacogenetic research results to breastfeeding mothers taking codeine: a pilot study of perceptions and benefits.

    PubMed

    Madadi, P; Joly, Y; Avard, D; Chitayat, D C; Smith, M A; Ross, C J D; Carleton, B C; Hayden, M R; Koren, G

    2010-12-01

    Sixty-two codeine-prescribed breastfeeding mothers from a pharmacogenetic study were interviewed regarding the communication of individual CYP2D6 genotype results and overall research findings. All participants wanted to receive the results of their individual genetic tests; however, individuals placed different values on the usefulness of this information toward future medical decisions. Receiving one's pharmacogenetic test results was not associated with a negative psychosocial impact. Thirty-three percent of the participants wished to withhold these results from their physicians. Participants' expectations seem to dictate the extent of transparency of pharmacogenetic research results. PMID:20739920

  17. The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

    PubMed

    Grayson, David S; Bliss-Moreau, Eliza; Machado, Christopher J; Bennett, Jeffrey; Shen, Kelly; Grant, Kathleen A; Fair, Damien A; Amaral, David G

    2016-07-20

    Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes.

  18. The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

    PubMed

    Grayson, David S; Bliss-Moreau, Eliza; Machado, Christopher J; Bennett, Jeffrey; Shen, Kelly; Grant, Kathleen A; Fair, Damien A; Amaral, David G

    2016-07-20

    Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes. PMID:27477019

  19. Clinical implementation of pharmacogenetics.

    PubMed

    García-González, Xandra; Cabaleiro, Teresa; Herrero, María José; McLeod, Howard; López-Fernández, Luis A

    2016-03-01

    In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not been as fast as desirable. The current situation of clinical implementation of pharmacogenetics is discussed. This review focuses on the advances of pharmacogenomics to individualize cancer treatments, the relationship between pharmacogenetics and pharmacodynamics in the clinical course of transplant patients receiving a combination of immunosuppressive therapy, the needs and barriers facing pharmacogenetic clinical application, and the situation of pharmacogenetic testing in Spain. It is based on lectures presented by speakers of the Clinical Implementation of Pharmacogenetics Symposium at the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held in April 20, 2015. PMID:26751902

  20. Pharmacogenetics, race and global injustice.

    PubMed

    Holm, Søren

    2008-08-01

    This paper discusses the link between pharmacogenetics and race, and the global justice issues that the introduction of pharmacogenetics in pharmaceutical research and clinical practice will raise. First, it briefly outlines the likely impact of pharmacogenetics on pharmaceutical research and clinical practice within the next five to ten years and then explores the link between pharmacogenetic traits and 'race'. It is shown that any link between apparent race and pharmacogenetics is problematic and that race cannot be used as a proxy for pharmacogenetic knowledge. The final section considers the implications of the development of pharmacogenetics for health care systems in low- and middle-income countries. PMID:19143085

  1. Risk, Reward, and the Double-Edged Sword: Perspectives on Pharmacogenetic Research and Clinical Testing Among Alaska Native People

    PubMed Central

    Robinson, Renee; Starks, Helene; Burke, Wylie; Dillard, Denise A.

    2013-01-01

    Objectives. Pharmacogenetic research and clinical testing raise important concerns for individuals and communities, especially where past medical research and practice has perpetrated harm and cultivated distrust of health care systems and clinicians. We investigated perceptions of pharmacogenetics among Alaska Native (AN) people. Methods. We held four focus groups for 32 ANs in south central Alaska to elicit views about pharmacogenetics in general and for treatment of cardiovascular disease, breast cancer, depression, and nicotine addiction. We analyzed data for perceived risks and rewards of pharmacogenetics. Results. Potential risks of pharmacogenetics included health care rationing, misuse of information, and stigma to individuals and the AN community. Potential rewards included decreased care costs, improved outcomes, and community development. Participants also discussed 8 contingent conditions that could mitigate risks and increase pharmacogenetic acceptability. Conclusions. Alaska Natives perceive pharmacogenetics as potentially benefitting and harming individuals, communities, and health systems, depending on methods and oversight. Researchers, clinicians, and administrators, especially in community-based clinic and health care systems serving minority populations, must address this “double-edged sword” to effectively conduct pharmacogenetics. PMID:24134351

  2. Pharmacogenetics in psychiatry: translating research into clinical practice

    PubMed Central

    Malhotra, AK; Zhang, J-P; Lencz, T

    2012-01-01

    Pharmacogenetic/pharmacogenomic (PGx) approaches to psychopharmacology aim to identify clinically meaningful predictors of drug efficacy and/or side-effect burden. To date, however, PGx studies in psychiatry have not yielded compelling results, and clinical utilization of PGx testing in psychiatry is extremely limited. In this review, the authors provide a brief overview on the status of PGx studies in psychiatry, review the commercialization process for PGx tests and then discuss methodological considerations that may enhance the potential for clinically applicable PGx tests in psychiatry. The authors focus on design considerations that include increased ascertainment of subjects in the earliest phases of illness, discuss the advantages of drug-induced adverse events as phenotypes for examination and emphasize the importance of maximizing adherence to treatment in pharmacogenetic studies. Finally, the authors discuss unique aspects of pharmacogenetic studies that may distinguish them from studies of other complex traits. Taken together, these data provide insights into the design and methodological considerations that may enhance the potential for clinical utility of PGx studies. PMID:22083729

  3. Pharmacogenetic Predictors of Response.

    PubMed

    Hertz, Daniel L; Rae, James M

    2016-01-01

    Pharmacogenetics attempts to predict treatment response using a patient's "germline" genome as the biomarker of interest. This chapter on pharmacogenetic predictors of breast cancer response is divided into four sections. The first introduces readers to genetic variation and describes how variation in the germline genome can affect biology or pharmacology. The second section introduces the translational pathway for pharmacogenetic research and discusses the specific challenges to identifying pharmacogenetic predictors of breast cancer response. The third section is divided into three subsections, each of which discusses a distinct category of pharmacogenetic response predictors; pharmacokinetics, cancer cell sensitivity, and effector cell activation. Within each subsection a specific pharmacogenetic association is described in detail; CYP2D6-tamoxifen, BRCA-PARP inhibitors, and FCGRA-trastuzumab, respectively, followed by a general discussion of other less well-established examples or areas for further research. The chapter concludes with a summary of the current status of pharmacogenetic predictors of breast cancer response and a few predictions for the future of this field.

  4. Pharmacogenetic Predictors of Response.

    PubMed

    Hertz, Daniel L; Rae, James M

    2016-01-01

    Pharmacogenetics attempts to predict treatment response using a patient's "germline" genome as the biomarker of interest. This chapter on pharmacogenetic predictors of breast cancer response is divided into four sections. The first introduces readers to genetic variation and describes how variation in the germline genome can affect biology or pharmacology. The second section introduces the translational pathway for pharmacogenetic research and discusses the specific challenges to identifying pharmacogenetic predictors of breast cancer response. The third section is divided into three subsections, each of which discusses a distinct category of pharmacogenetic response predictors; pharmacokinetics, cancer cell sensitivity, and effector cell activation. Within each subsection a specific pharmacogenetic association is described in detail; CYP2D6-tamoxifen, BRCA-PARP inhibitors, and FCGRA-trastuzumab, respectively, followed by a general discussion of other less well-established examples or areas for further research. The chapter concludes with a summary of the current status of pharmacogenetic predictors of breast cancer response and a few predictions for the future of this field. PMID:26987536

  5. The communication of pharmacogenetic research results: participants weigh in on their informational needs in a pilot study.

    PubMed

    Madadi, Parvaz; Joly, Yann; Avard, Denise; Chitayat, David C; Smith, M Anne; D Ross, Colin J; Carleton, Bruce C; Hayden, Michael R; Koren, Gideon

    2011-01-01

    In this brief investigation, the informational needs of research participants [n = 62; mothers who had breastfed, taken codeine, and participated in a pharmacogenetic study] were probed during a counselling session in which they received their CYP2D6 pharmacogenetic research results and overall study results. In addition to the standard information, developed by a multidisciplinary team and provided to the participants, 38% of individuals had further questions related to potential adverse effects in babies, future codeine or medication use, heredity, and consequences for policies and programmes. The diversity and complexity of the questions raised support the need to communicate the results in the context of personalized genetic counselling information sessions. PMID:21467605

  6. Pharmacogenetics and personal genomes

    PubMed Central

    Wagner, Michael J

    2010-01-01

    While pharmacogenetics - the correlation of genotype and response to medicines - currently has a small but measurable impact on the prescribing practice of clinicians, the advent of the `personal genome' is likely to change this significantly. Advances in high-throughput technologies aimed at characterizing human genetic variation, including chip-based genotyping and next-generation sequencing, are poised to provide a flood of information that will affect both pharmacogenetic discovery and pharmacogenetic application in clinical practice. In order for this flood of information to not overwhelm both researchers and clinicians alike, a variety of new and expanded information management tools will be needed, including electronic medical records, bioinformatic algorithms for analyzing sequence data, information management systems for storing, retrieving and interpreting whole-genome sequence data, and pharmacogenetic decision tools for prescribers. PMID:20190862

  7. Pharmacogenetic information for patients on drug labels.

    PubMed

    Haga, Susanne B; Mills, Rachel; Moaddeb, Jivan

    2014-01-01

    Advances in pharmacogenetic research have improved our understanding of adverse drug responses and have led to the development of pharmacogenetic tests and targeted drugs. However, the extent of the communication process and provision of information to patients about pharmacogenetics is unclear. Pharmacogenetic information may be included in sections of a drug's package insert intended for patients, which is provided directly to patients or communicated via the health provider. To determine what pharmacogenetic information, if any, is included in patient-targeted sections of the drug label, we reviewed the labels listed in the US Food and Drug Administration's Table of Pharmacogenomic Biomarkers in Drug Labels. To date, 140 drugs include pharmacogenetic-related information in the approved label. Our analysis revealed that pharmacogenetic information is included in patient-targeted sections for a minority (n=29; 21%) of drug labels, with no obvious pattern associated with the inclusion of pharmacogenetic information. Therefore, patients are unlikely to learn about pharmacogenetics through written materials dispensed with the drug. Given that there are also inconsistencies with regard to inclusion of pharmacogenetic information in the patient counseling information section, it is also unlikely that patients are receiving adequate pharmacogenetic information from their provider. The inconsistent presence of pharmacogenetic information in patient-targeted sections of drug labels suggests a need to review the criteria for inclusion of information in patient-targeted sections in order to increase consistency and patient knowledge of pharmacogenetic information. PMID:25342916

  8. Pharmacogenetic information for patients on drug labels

    PubMed Central

    Haga, Susanne B; Mills, Rachel; Moaddeb, Jivan

    2014-01-01

    Advances in pharmacogenetic research have improved our understanding of adverse drug responses and have led to the development of pharmacogenetic tests and targeted drugs. However, the extent of the communication process and provision of information to patients about pharmacogenetics is unclear. Pharmacogenetic information may be included in sections of a drug’s package insert intended for patients, which is provided directly to patients or communicated via the health provider. To determine what pharmacogenetic information, if any, is included in patient-targeted sections of the drug label, we reviewed the labels listed in the US Food and Drug Administration’s Table of Pharmacogenomic Biomarkers in Drug Labels. To date, 140 drugs include pharmacogenetic-related information in the approved label. Our analysis revealed that pharmacogenetic information is included in patient-targeted sections for a minority (n=29; 21%) of drug labels, with no obvious pattern associated with the inclusion of pharmacogenetic information. Therefore, patients are unlikely to learn about pharmacogenetics through written materials dispensed with the drug. Given that there are also inconsistencies with regard to inclusion of pharmacogenetic information in the patient counseling information section, it is also unlikely that patients are receiving adequate pharmacogenetic information from their provider. The inconsistent presence of pharmacogenetic information in patient-targeted sections of drug labels suggests a need to review the criteria for inclusion of information in patient-targeted sections in order to increase consistency and patient knowledge of pharmacogenetic information. PMID:25342916

  9. Pharmacogenetics: ethical issues and policy options.

    PubMed

    Buchanan, Allen; Califano, Andrea; Kahn, Jeffrey; McPherson, Elizabeth; Robertson, John; Brody, Baruch

    2002-03-01

    Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.

  10. Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics).

    PubMed

    Fricke-Galindo, Ingrid; Jung-Cook, Helgi; LLerena, Adrián; López-López, Marisol

    2016-06-01

    Mexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico's population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of CYP2D6*3, *4, *5, *10, *17, *35 and *41 alleles in the MM group were different from those reported in the MI group. CYP2C9*2 and *3 alleles were more frequent in MM than in MI populations (χ2 test, p<0.05). CYP2C19*3 allele was not found in the MM or MI populations reported. For UGT1A1*28, only one study was found. HLA-A*31:01 and HLA-B*15:02 were present in some MM and MI populations. Poor metabolizers for CYP2D6 and CYP2C9 were more frequent in MM than in MI groups (χ2 test, p<0.05). Only 26% of the relevant pharmacogenetic biomarkers searched have been studied in Mexican healthy volunteers; therefore, further studies are warranted. The frequency variation of biomarkers in MM and MI populations could be important for the clinical implementation of pharmacogenetics in Mexico.

  11. Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics).

    PubMed

    Fricke-Galindo, Ingrid; Jung-Cook, Helgi; LLerena, Adrián; López-López, Marisol

    2016-06-01

    Mexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico's population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of CYP2D6*3, *4, *5, *10, *17, *35 and *41 alleles in the MM group were different from those reported in the MI group. CYP2C9*2 and *3 alleles were more frequent in MM than in MI populations (χ2 test, p<0.05). CYP2C19*3 allele was not found in the MM or MI populations reported. For UGT1A1*28, only one study was found. HLA-A*31:01 and HLA-B*15:02 were present in some MM and MI populations. Poor metabolizers for CYP2D6 and CYP2C9 were more frequent in MM than in MI groups (χ2 test, p<0.05). Only 26% of the relevant pharmacogenetic biomarkers searched have been studied in Mexican healthy volunteers; therefore, further studies are warranted. The frequency variation of biomarkers in MM and MI populations could be important for the clinical implementation of pharmacogenetics in Mexico. PMID:26812836

  12. [Pharmacogenetic research in the association between human leukocyte antigen and adverse drug reactions].

    PubMed

    Xiong, Yan; Zhang, Wei; Chen, Xiaoping

    2014-07-01

    With the rapid development of pharmacogenetics, more and more studies have shown evidence in the association between polymorphisms at the human leukocyte antigen (HLA) loci and severe adverse drug reactions (SADRs). Several HLA-B alleles proved to be associated with SADRs for drugs such as carbamazepine, allopurinol, lamotrigine, and flucloxacillin. The USA Food and Drug Administration (FDA) has even recommended routine screening for HLA-B allele before the use of abacavir and carbamazepine. With the completion of human genome project and the Hapmap project, several new pharmacogenetics approaches such as genome-wide association study (GWAS) have emerged. These newly developed methods will undoubtedly accelerate the identification and clinical utilization of the pharmacogenetic biomakers. In addition, the immunogenetic mechanisms by which the HLA alleles cause SADRs are explored at the cellular and molecular level. This review focuses on the recent progresses in HLA alleles and ADRs regarding both the clinical translation and modern pharmacogenetic methods. PMID:25080918

  13. Special populations and pharmacogenetic issues in tuberculosis drug development and clinical research.

    PubMed

    McIlleron, Helen; Abdel-Rahman, Susan; Dave, Joel Alex; Blockman, Marc; Owen, Andrew

    2015-06-15

    Special populations, including children and pregnant women, have been neglected in tuberculosis drug development. Patients in developing countries are inadequately represented in pharmacology research, and postmarketing pharmacovigilance activities tend to be rudimentary in these settings. There is an ethical imperative to generate evidence at an early stage to support optimal treatment in these populations and in populations with common comorbid conditions, such as diabetes and human immunodeficiency virus (HIV) infection. This article highlights the research needed to support equitable access to new antituberculosis regimens. Efficient and opportunistic pharmacokinetic study designs, typically using sparse sampling and population analysis methods, can facilitate optimal dose selection for children and pregnant women. Formulations suitable for children should be developed early and used in pharmacokinetic studies to guide dose selection. Drug-drug interactions between commonly coprescribed medications also need to be evaluated, and when these are significant, alternative approaches should be sought. A potent rifamycin-sparing regimen could revolutionize the treatment of adults and children requiring a protease inhibitor as part of antiretroviral treatment regimens for HIV infection. A sufficiently wide formulary of drugs should be developed for those with contraindications to the standard approaches. Because genetic variations may influence an individual's response to tuberculosis treatment, depending on the population being treated, it is important that samples be collected and stored for pharmacogenetic study in future clinical trials. PMID:26009615

  14. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years

    PubMed Central

    Panczyk, Mariusz

    2014-01-01

    During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation, as a result of large international research projects (Human Genome Project, the 1000 Genomes Project International HapMap Project, and Programs for Genomic Applications NHLBI-PGA). This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer. For clinical use in the treatment of patients with colorectal cancer (CRC), in addition to fluoropyrimidines, another two new cytostatic drugs were allowed: irinotecan and oxaliplatin. Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted. The last 20 years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance. One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells. Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine. Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics. Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential. This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy. The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review. PMID:25110414

  15. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years.

    PubMed

    Panczyk, Mariusz

    2014-08-01

    During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation, as a result of large international research projects (Human Genome Project, the 1000 Genomes Project International HapMap Project, and Programs for Genomic Applications NHLBI-PGA). This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer. For clinical use in the treatment of patients with colorectal cancer (CRC), in addition to fluoropyrimidines, another two new cytostatic drugs were allowed: irinotecan and oxaliplatin. Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted. The last 20 years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance. One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells. Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine. Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics. Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential. This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy. The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review.

  16. Pharmacogenetics of antihypertensive drug response.

    PubMed

    Kreutz, Reinhold

    2004-02-01

    Pharmacogenetics is a discipline of molecular medicine that investigates the genetic basis of individual variation of drug responses. Before the era of the human genome project and the subsequent progress in genomic research, this field was primarily restricted to the investigation of the genetics of drug-metabolizing enzymes as they account for individual differences in pharmacokinetics and tolerability of drugs. In the current genomic era, pharmacogenetic research is applied to all fields of drug treatment in clinical medicine, including hypertension research. In contrast to the traditional approach, however, the influence of individual genetic variation on the efficacy of a drug (ie, the pharmacodynamic response) is the major focus of pharmacogenetic research and its clinical applicability. Therefore, the identification of individual genetic variation influencing the blood pressure-lowering effect of an antihypertensive compound and the implementation of this knowledge into clinical practice is the major goal of pharmacogenetic research in the field of hypertension. In this article, some important, recent research work and progress on the pharmacogenetics of antihypertensive drug responses are reviewed and evaluated. PMID:14972084

  17. Pharmacogenetics, pharmacogenomics and ecogenetics.

    PubMed

    Motulsky, Arno G; Qi, Ming

    2006-02-01

    Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.

  18. Amodiaquine pharmacogenetics.

    PubMed

    Gil, Jose Pedro

    2008-10-01

    Amodiaquine is a central drug in the new global strategy of combination therapies for the control of malaria. Amodiaquine is mainly metabolized hepatically towards its major active metabolite desethylamodiaquine, by the polymorphic P450 isoform CYP2C8. Amodiaquine is associated with rare but serious side effects, as well as with relatively frequent mild ones. These are expected to be at least partially related to CYP2C8 alleles. Pharmacogenetic knowledge of amodiaquine exposed populations is important for pharmacovigilance issues and in being a first step for future realistic applications from a personal medicine perspective.

  19. Pharmacogenetics of antipsychotic treatment in schizophrenia.

    PubMed

    Pouget, Jennie G; Müller, Daniel J

    2014-01-01

    Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research, and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach.In this chapter, we provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings are presented for both antipsychotic response and commonly studied adverse reactions. The application of pharmacogenetics to schizophrenia treatment is discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research.

  20. Pharmacogenetics of OPRM1.

    PubMed

    Crist, Richard C; Berrettini, Wade H

    2014-08-01

    Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. The OPRM1 gene has been a target of interest in a large number of pharmacogenetic studies due to its genetic and structural variation, as well as the role of opioid receptors in a variety of disorders. The mu-opioid receptor (MOR), encoded by OPRM1, naturally regulates the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic variants in OPRM1, particularly the non-synonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPRM1, primarily with regard to the treatment of pain and addiction. PMID:24201053

  1. Pharmacogenetics of OPRM1

    PubMed Central

    Crist, Richard C.; Berrettini, Wade H.

    2013-01-01

    Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. The OPRM1 gene has been a target of interest in a large number of pharmacogenetic studies due to its genetic and structural variation, as well as the role of opioid receptors in a variety of disorders. The mu-opioid receptor (MOR), encoded by OPRM1, naturally regulates the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic variants in OPRM1, particularly the nonsynonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPMR1, primarily in regards to the treatment of pain and addiction. PMID:24201053

  2. Pharmacogenetics of OPRM1.

    PubMed

    Crist, Richard C; Berrettini, Wade H

    2014-08-01

    Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. The OPRM1 gene has been a target of interest in a large number of pharmacogenetic studies due to its genetic and structural variation, as well as the role of opioid receptors in a variety of disorders. The mu-opioid receptor (MOR), encoded by OPRM1, naturally regulates the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic variants in OPRM1, particularly the non-synonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPRM1, primarily with regard to the treatment of pain and addiction.

  3. Pharmacogenetics of inflammatory bowel disease.

    PubMed

    Katsanos, Konstantinos H; Papadakis, Konstantinos A

    2014-12-01

    Pharmacogenetic studies have been performed for almost all classes of drugs that have been used in IBD but very few have generated consistent findings or have been replicated. The genetic test that has been approved for clinical practice is TPMT testing prior to starting treatment with thiopurine drugs. Research in IBD pharmacogenetics has focused on prediction of drug efficacy and toxicity by identifying polymorphisms in the genes encoding enzymes that are involved in metabolic pathways. Recent research has mainly focused on therapeutic agents such as azathioprine, methotrexate, aminosalicylates, corticosteroids, infliximab and adalimumab. Future pharmaceutical trials should include pharmacogenetic research to test appropriate candidate genes in a prospective manner and correlate genetic associations with trial outcomes and relevant functional data. PMID:25521361

  4. Pharmacogenetics of inflammatory bowel disease.

    PubMed

    Katsanos, Konstantinos H; Papadakis, Konstantinos A

    2014-12-01

    Pharmacogenetic studies have been performed for almost all classes of drugs that have been used in IBD but very few have generated consistent findings or have been replicated. The genetic test that has been approved for clinical practice is TPMT testing prior to starting treatment with thiopurine drugs. Research in IBD pharmacogenetics has focused on prediction of drug efficacy and toxicity by identifying polymorphisms in the genes encoding enzymes that are involved in metabolic pathways. Recent research has mainly focused on therapeutic agents such as azathioprine, methotrexate, aminosalicylates, corticosteroids, infliximab and adalimumab. Future pharmaceutical trials should include pharmacogenetic research to test appropriate candidate genes in a prospective manner and correlate genetic associations with trial outcomes and relevant functional data.

  5. Pharmacogenetics in the brazilian population.

    PubMed

    Suarez-Kurtz, Guilherme

    2010-01-01

    Brazil is the fifth largest country in the world and its present population, in excess of 190;million, is highly heterogeneous, as a result of centuries of admixture between Amerindians, Europeans, and Sub-Saharan Africans. The estimated individual proportions of biogeographical ancestry vary widely and continuously among Brazilians: most individuals, irrespective of self-identification as White, Brown or Black - the major categories of the Brazilian Census "race/color" system - have significant degrees of European and African ancestry, while a sizeable number display also Amerindian ancestry. These features have important pharmacogenetic (PGx) implications: first, extrapolation of PGx data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in pharmacogenes (e.g., CYP3A5, CYP2C9, GSTM1, ABCB1, GSTM3, VKORC, etc) varies continuously among Brazilians and is not captured by race/color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. The peculiarities of PGx in Brazilians are illustrated with data for different therapeutic groups, such as anticoagulants, HIV protease inhibitors and non-steroidal antinflammatory drugs, and the challenges and advantages created by population admixture for the study and implementation of PGx are discussed. PGx data for Amerindian groups and Brazilian-born, first-generation Japanese are presented to illustrate the rich diversity of the Brazilian population. Finally, I introduce the reader to the Brazilian Pharmacogenetic Network or Refargen, a nation-wide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population health impact. PMID:21833165

  6. Pharmacogenetics in the Brazilian Population

    PubMed Central

    Suarez-Kurtz, Guilherme

    2010-01-01

    Brazil is the fifth largest country in the world and its present population, in excess of 190;million, is highly heterogeneous, as a result of centuries of admixture between Amerindians, Europeans, and Sub-Saharan Africans. The estimated individual proportions of biogeographical ancestry vary widely and continuously among Brazilians: most individuals, irrespective of self-identification as White, Brown or Black – the major categories of the Brazilian Census “race/color” system – have significant degrees of European and African ancestry, while a sizeable number display also Amerindian ancestry. These features have important pharmacogenetic (PGx) implications: first, extrapolation of PGx data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in pharmacogenes (e.g., CYP3A5, CYP2C9, GSTM1, ABCB1, GSTM3, VKORC, etc) varies continuously among Brazilians and is not captured by race/color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. The peculiarities of PGx in Brazilians are illustrated with data for different therapeutic groups, such as anticoagulants, HIV protease inhibitors and non-steroidal antinflammatory drugs, and the challenges and advantages created by population admixture for the study and implementation of PGx are discussed. PGx data for Amerindian groups and Brazilian-born, first-generation Japanese are presented to illustrate the rich diversity of the Brazilian population. Finally, I introduce the reader to the Brazilian Pharmacogenetic Network or Refargen1, a nation-wide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population health impact. PMID:21833165

  7. Pharmacogenetics of Response to Statins

    PubMed Central

    Zineh, Issam

    2016-01-01

    The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) are among the most commonly prescribed drugs worldwide. On average, statins improve lipid profiles and have been shown to have ancillary beneficial effects on inflammation, platelet activity, and endothelial function. However, variability in drug response exists regardless of the measured phenotype, and genetic variability may be a contributing factor. Recently, there has been an interesting shift in statin pharmacogenetic studies. Novel study designs have been employed and nontraditional candidate genes have been investigated in relation to both lipid and nonlipid responses to statins. This review outlines earlier pharmacogenetic studies and highlights newly published findings that expand on previous work. Furthermore, a framework is provided in which the necessary next steps in research are described, with the ultimate goal of translating pharmacogenetic findings into clinically meaningful changes in patient care. PMID:18241612

  8. Pharmacogenetics and individualizing drug treatment during pregnancy

    PubMed Central

    Haas, David M

    2014-01-01

    Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs. PMID:24329192

  9. Pharmacogenetics and individualizing drug treatment during pregnancy.

    PubMed

    Haas, David M

    2014-01-01

    Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs.

  10. Pharmacogenetics and pharmacoepidemiology.

    PubMed

    Jones, J K

    2001-01-01

    This paper seeks to stimulate consideration of the short- and long-term possibilities raised by research into pharmacogenetics and pharmacoepidemiology, to identify potential tissue databanks linked to population data, and to summarize our ethical responsibilities. Short term, we might identify selected disorders or risk factors, such as for drug-associated serious events, and might find selected target populations. Long term, we might incorporate genomics techniques into population data and map genetic risk factors for diseases and drug responses. Tissue specimens that might be linked to clinical data lie in certain data resources: clinical trials, ad hoc cohorts, case registries, and cross-sectional and longitudinal population samples. Specific areas must be addressed in research using human tissue and genetic material, including the ethical threat to privacy. We must avoid misuse of genetic information by breaching confidentiality and putting at risk specific genetically identifiable groups. The National Bioethics Advisory Commission recently addressed the issue of serum and tissue data banks in a published report summarized in this paper. Social, methodologic, and ethical issues relate to any protocol using serum and tissue, and indicate a need for broad educational efforts. We must set guidelines as pharmacogenetics research becomes a dimension of pharmacoepidemiology.

  11. [Networks in cognitive research].

    PubMed

    Pléh, Csaba

    2012-01-01

    This review paper starts from discussing two models of network research: one starting from general networks, the other starting from the Ego. Ego based researches are characterized starting form the model of Dunbar as presenting networks of different size and intimacy, both in real and virtual networks. Researches into the personality determinants of networks mainly shows the effects of extroversion. The future of network research indicates a trend towards relating personal, conceptual, and neural networks.

  12. Progress in pharmacogenetics: consortiums and new strategies.

    PubMed

    Maroñas, Olalla; Latorre, Ana; Dopazo, Joaquín; Pirmohamed, Munir; Rodríguez-Antona, Cristina; Siest, Gérard; Carracedo, Ángel; LLerena, Adrián

    2016-03-01

    Pharmacogenetics (PGx), as a field dedicated to achieving the goal of personalized medicine (PM), is devoted to the study of genes involved in inter-individual response to drugs. Due to its nature, PGx requires access to large samples; therefore, in order to progress, the formation of collaborative consortia seems to be crucial. Some examples of this collective effort are the European Society of Pharmacogenomics and personalized Therapy and the Ibero-American network of Pharmacogenetics. As an emerging field, one of the major challenges that PGx faces is translating their discoveries from research bench to bedside. The development of genomic high-throughput technologies is generating a revolution and offers the possibility of producing vast amounts of genome-wide single nucleotide polymorphisms for each patient. Moreover, there is a need of identifying and replicating associations of new biomarkers, and, in addition, a greater effort must be invested in developing regulatory organizations to accomplish a correct standardization. In this review, we outline the current progress in PGx using examples to highlight both the importance of polymorphisms and the research strategies for their detection. These concepts need to be applied together with a proper dissemination of knowledge to improve clinician and patient understanding, in a multidisciplinary team-based approach. PMID:26913460

  13. Pharmacogenetics of antidepressant response.

    PubMed

    Keers, Robert; Aitchison, Katherine J

    2011-01-01

    There is substantial interindividual variation in response to antidepressants. Family and twin studies suggest that genetic variation may, at least in part, explain these differences. Pharmacogenetic research attempts to identify the genetic variants associated with antidepressant response to both understand the mechanism of action of pharmacotherapies and to predict outcome. Genes implicated in the pharmacokinetics or pharmacodyamics of antidepressants have been shown to predict response; however, the failure of some findings to replicate has been disappointing. More recent hypothesis-free approaches have identified novel candidates for antidepressant response. However, results have been considerably modest and suggest that treatment outcome is determined by multiple genetic variants of small effect. The small effect sizes of genetic variants and heterogeneity between studies have significantly hindered attempts to find robust genetic predictors of response to antidepressants. To allow the direct comparison of findings, future pharmacogenetic studies should employ standardized methodology and consider using intermediate phenotypes of response, such as neurogenesis, that may more closely reflect the mechanism of action of antidepressants. PMID:21158559

  14. Pharmacogenetics in Ghana: reviewing the evidence.

    PubMed

    Kudzi, W; Adjei, G O; Ofori-Adjei, D; Dodoo, A N O

    2011-06-01

    Different clinical response of different patients to the same medicine has been recognised and documented since the 1950's. Variability in response of individuals to standard doses of drug therapy is important in clinical practice and can lead to therapeutic failures or adverse drug reactions. Pharmacogenetics seeks to identify individual genetic differences (polymorphisms) in drug absorption, metabolism, distribution and excretion that can affect the activity of a particular drug with the view of improving efficacy and reducing toxicity. Although knowledge of pharmacogenetics is being translated into clinical practice in the developed world, its applicability in the developing countries is low. Several factors account for this including the fact that there is very little pharmacogenetic information available in many indigenous African populations including Ghanaians. A number of genes including Cytochrome P450 (CYP) 2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, MDR1 and TPMT have been genotyped in the Ghanaian population since the completion of the Human genome project. There is however, an urgent need to increase pharmacogenetic research in Ghana to increase availability of data. Introducing Pharmacogenetics into the curriculum of Medical and Pharmacy training institutions will influence translating knowledge of pharmacogenetics into clinical practice. This will also equip health professionals with the skill to integrate genetic information into public health decision making. PMID:21857725

  15. Pharmacogenetics of new analgesics

    PubMed Central

    Lötsch, Jörn; Geisslinger, Gerd

    2011-01-01

    Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2) or associated signalling pathways (KCNJ6). Translational and genetic research have identified new targets, for which new analgesics are being developed. This addresses voltage-gated sodium, calcium and potassium channels, for which SCN9A, CACNA1B, KCNQ2 and KCNQ3, respectively, are primary gene candidates because they code for the subunits of the respective channels targeted by analgesics currently in clinical development. Mutations in voltage gated transient receptor potential (TRPV) channels are known from genetic pain research and may modulate the effects of analgesics under development targeting TRPV1 or TRPV3. To this add ligand-gated ion channels including nicotinic acetylcholine receptors, ionotropic glutamate-gated receptors and ATP-gated purinergic P2X receptors with most important subunits coded by CHRNA4, GRIN2B and P2RX7. Among G protein coupled receptors, δ-opioid receptors (coded by OPRD1), cannabinoid receptors (CNR1 and CNR2), metabotropic glutamate receptors (mGluR5 coded by GRM5), bradykinin B1 (BDKRB1) and 5-HT1A (HTR1A) receptors are targeted by new analgesic substances. Finally, nerve growth factor (NGFB), its tyrosine kinase receptor (NTRK1) and the fatty acid amide hydrolase (FAAH) have become targets of interest. For most of these genes, functional variants have been associated with neuro-psychiatric disorders and not yet with analgesia. However, research on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics. The increased number of candidate pharmacogenetic modulators of analgesic actions may open opportunities for the broader clinical implementation of genotyping information. PMID:20942817

  16. Population pharmacogenetics of Ibero-Latinoamerican populations (MESTIFAR 2014).

    PubMed

    Sosa-Macias, Martha; Moya, Graciela E; LLerena, Adrián; Ramírez, Ronald; Terán, Enrique; Peñas-LLedó, Eva M; Tarazona-Santos, Eduardo; Galaviz-Hernández, Carlos; Céspedes-Garro, Carolina; Acosta, Hildaura

    2015-01-01

    MESTIFAR 2014 28-30 November 2014, Panama City, Panama The CEIBA consortium was created within the Ibero-American network of Pharmacogenetics (RIBEF) to study population pharmacogenetics. The current status of these initiatives and results of the MESTIFAR project were analyzed in Panama, 28-30 November 2014. The MESTIFAR project focused on studying CYPs genetic polymorphisms in populations of different ethnic origin. So far, more than 6000 healthy volunteers have been evaluated, making this one of the largest population pharmacogenomic studies worldwide. Three symposia were organized, 'Pharmacogenetics of indigenous and mestizos populations and its clinical implications', 'Methodological innovation in pharmacogenetics and its application in health', and 'General discussion and concluding remarks', about mechanisms and proposals for training, diffusion of pharmacogenetics for Spanish- and Portuguese-speaking health professionals, and 'bench to bedside' pilot projects.

  17. Pharmacogenetics--legal, ethical and regulatory considerations.

    PubMed

    March, R; Cheeseman, K; Doherty, M

    2001-11-01

    The overall objective of pharmacogenetics is to determine the genetic basis of variability in drug efficacy and safety, and to use this information to benefit the patient. Genetics can be used to develop drugs that are suitable for the majority of patients and to help identify those patients for whom a certain drug may not be the most appropriate. This review will cover some background to pharmacogenetics and various issues including confidentiality, data protection, coding of samples and genetic data, informed consent, and drug development guidelines. International, national and regional variation in the legal and regulatory basis for pharmacogenetics presents challenges for researchers attempting to increase scientific understanding in the field. Examples of national and international regulations and guidelines will be given. It is clear that pharmacogenetics today is a long way from the 'personalised medicine' advocated by some individuals in recent years. The aim of pharmacogenetic research should always be to make sure that patients have the best treatment available and that patients are not exposed to drugs to which they are genetically unable to respond. This vision must continue to inspire researchers and regulators who are working together to make it a widespread reality.

  18. Clinical implications of opioid pharmacogenetics.

    PubMed

    Argoff, Charles E

    2010-01-01

    The peer-reviewed literature yields a plethora of examples of variability in patient's responses to medications. The rapidly progressing field of pharmacogenetics offers insight into the variation in responses observed clinically, and in particular for the variability observed among patients administered mu opioid analgesics. Genetic variation leads to interperson variability in drug absorption, distribution, metabolism, and excretion, processes that have an important impact on the observed efficacy and toxicity of a drug. In particular, single-nucleotide polymorphisms (SNPs) in the gene encoding the mu opioid receptor have been linked to the variability in responses to opioids, whereas SNPs within metabolic enzymes that process and eliminate opioids and their metabolites also have an important effect on an individual's response to opioid medications as do SNPs that affect the bioavailability of opioids. In current clinical practice, given the best available evidence, to optimize pain medications each patient is, in effect, given their own analgesic trial. In the near future, pharmacogenetic approaches may be implemented to best predict which medicine from the outset may be most appropriate for an individual-the therapy with the most sustained efficacy and the best side effect profile. In the meantime, pharmacogenetic studies on mu opioid analgesics have provided a molecular foundation supporting opioid rotation in cases in which opioid therapy loses efficacy or becomes associated with intolerable side effects. As more pharmacogenetic research links specific polymorphisms to the pharmacologic effects of specific opioid analgesics, clinicians will continue to improve their understanding of how to prescribe these medications more effectively. PMID:20026961

  19. Pharmacogenetics of cardiovascular drug therapy

    PubMed Central

    Peters, Bas J.M.; Klungel, Olaf H.; de Boer, Anthonius; Ch. Stricker, Bruno H.; Maitland-van der Zee, Anke-Hilse

    2009-01-01

    In developed countries cardiovascular disease is one of the leading causes of death. Cardiovascular drugs such as platelet aggregation inhibitors, oral anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly prescribed to reduce risk of cardiovascular disease. Notable interindividual variation exists in the response to these pharmacotherapeutic interventions, which can be partially explained by factors such as gender, age, diet, concomitant drug use and environmental factors. Notwithstanding, a great part of this variability remains unknown. To a smaller or larger extent, genetic variability may contribute to the variability in response to these cardiovascular drugs. This review gives an overview of pharmacogenetic studies of genes that were reported to be associated with four commonly prescribed drugs/drug classes (platelet aggregation inhibitors, coumarins, antihypertensives and statins) and were studied at least 2 times with a similar outcome measure. In the field of cardiovascular drug therapy, polymorphisms in candidate genes such as the cycloxygenase-1, vitamin K reductase complex subunit 1, CYP2C9, alpha adducin and 3-hydroxy-3-methylglutaryl-CoA reductase have received a great amount of interest in the pharmacogenetics of aspirin, coumarins, antihypertensives and statins respectively. However, only variations in VKORC1 and CYP2C9 have consistently been associated with drug response (coumarins) and have clinical implications. Clinical trials should provide evidence for the effectiveness of genotyping before this procedure will be a part of every day anticoagulant therapy. In spite of the tremendous amount of publications in this field, there is no reason to advocate for genetic testing for any other drugs cardiovascular drug therapy yet. Current approaches in pharmacogenetic research do not seem to lead to results that meet our expectations of individualized medicine. Therefore, new approaches are needed addressing issues and

  20. Employing Dictyostelium as an Advantageous 3Rs Model for Pharmacogenetic Research.

    PubMed

    Otto, Grant P; Cocorocchio, Marco; Munoz, Laura; Tyson, Richard A; Bretschneider, Till; Williams, Robin S B

    2016-01-01

    Increasing concern regarding the use of animals in research has triggered a growing need for non-animal research models in a range of fields. The development of 3Rs (replacement, refinement, and reduction) approaches in research, to reduce the reliance on the use of animal tissue and whole-animal experiments, has recently included the use of Dictyostelium. In addition to not feeling pain and thus being relatively free of ethical constraints, Dictyostelium provides a range of distinct methodological advantages for researchers that has led to a number of breakthroughs. These methodologies include using cell behavior (cell movement and shape) as a rapid indicator of sensitivity to poorly characterized medicines, natural products, and other chemicals to help understand the molecular mechanism of action of compounds. Here, we outline a general approach to employing Dictyostelium as a 3Rs research model, using cell behavior as a readout to better understand how compounds, such as the active ingredient in chilli peppers, capsaicin, function at a cellular level. This chapter helps scientists unfamiliar with Dictyostelium to rapidly employ it as an advantageous model system for research, to reduce the use of animals in research, and to make paradigm shift advances in our understanding of biological chemistry. PMID:27271898

  1. Pharmacogenetics and Pharmacogenomics of Anticancer Agents

    PubMed Central

    Huang, R. Stephanie; Ratain, Mark J.

    2011-01-01

    Large interindividual variation is observed in both the response and toxicity associated with anticancer therapy. The etiology of this variation is multifactorial, but is due in part to host genetic variations. Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this variation in susceptibility to chemotherapy. This review provides an overview of the progress made in the field of pharmacogenetics and pharmacogenomics using a five-stage architecture, which includes 1) determining the role of genetics in drug response; 2) screening and identifying genetic markers; 3) validating genetic markers; 4) clinical utility assessment; and 5) pharmacoeconomic impact. Examples are provided to illustrate the identification, validation, utility, and challenges of these pharmacogenetic and pharmacogenomic markers, with the focus on the current application of this knowledge in cancer therapy. With the advance of technology, it becomes feasible to evaluate the human genome in a relatively inexpensive and efficient manner; however, extensive pharmacogenetic research and education are urgently needed to improve the translation of pharmacogenetic concepts from bench to bedside. PMID:19147868

  2. Pharmacogenetics in pancreatic cancer.

    PubMed

    Tourkantonis, Ioannis S; Peponi, Evangelia; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2014-07-01

    Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting. PMID:25076337

  3. Pharmacogenetics, ethical issues: review of the Nuffield Council on Bioethics Report.

    PubMed

    Corrigan, O P

    2005-03-01

    In September this year the Nuffield Council on Bioethics held a meeting to disclose and discuss the main findings of their newly published report on the ethical issues associated with developments in pharmacogenetics research. The basics of pharmacogenetics science is briefly outlined, and then the extent to which the report was successful in addressing (or at least highlighting) the attendant social, ethical, and policy implications of pharmacogenetics research is evaluated.

  4. The Pharmacogenetics of Alcohol Use Disorder

    PubMed Central

    Jones, Jermaine D.; Comer, Sandra D.; Kranzler, Henry R.

    2014-01-01

    Background Annually, the use and abuse of alcohol contributes to millions of deaths and billions of dollars in societ al costs. To determine the impact of genetic variation on the susceptibility to the disorder and its response to treatment, studies have been conducted to assess the contribution of a variety of candidate genetic variants. These variants, which we review here, were chosen based upon their observed or hypothesized functional relevance to AUD risk or to the mechanism by which medications used to treat the disorder exert their effects. Methods This qualitative review examines studies in which candidate polymorphisms were tested as moderator variables to identify pharmacogenetic effects on either the subjective response to alcohol or the outcomes of pharmacotherapy. Results Although findings from these studies provide evidence of a number of clinically relevant pharmacogenetic effects, the literature is limited and there are conflicting findings that require resolution. Conclusions Pharmacogenetic studies of AUD treatment that use greater methodological rigor and better statistical controls, such as corrections for multiple testing, may help to resolve inconsistent findings. These procedures could also lead to the discovery of more robust and clinically meaningful moderator effects. As the field evolves through methodological standardization and the use of larger study samples, pharmacogenetic research has the potential to inform clinical care by enhancing therapeutic effects and personalizing treatments. These efforts may also provide insights into the mechanisms by which medications reduce heavy drinking or promote abstinence in patients with an AUD. PMID:25703505

  5. Pharmacogenetics of Oral Antidiabetic Drugs

    PubMed Central

    Becker, Matthijs L.; Pearson, Ewan R.; Tkáč, Ivan

    2013-01-01

    Oral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins constituting ATP-sensitive K+ channel which is a therapeutic target for sulfonylureas, and TCF7L2 is a gene with the strongest association with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant near ATM gene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future. PMID:24324494

  6. Pharmacogenetics of Antipsychotics: Recent Progress and Methodological Issues

    PubMed Central

    Zhang, Jian-Ping; Malhotra, Anil K.

    2012-01-01

    Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences in clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one’s genetic markers. Areas covered in this review This article reviews the recent progress in pharmacogenetic research of antipsychotic drugs since 2010, focusing on two areas: antipsychotic-induced weight gain and clozapine-induced agranulocytosis. Important methodological issues in this area of research are discussed. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic studies of antipsychotic drugs are promising despite of many challenges. Recent advances as reviewed in this article push the field closer to routine clinical utilization of pharmacogenetic testing. Progress in genomic technology and bioinformatics, larger sample sizes, better phenotype characterization, and careful consideration of study design issues will help to elevate antipsychotic pharmacogenetics to its next level. PMID:23199282

  7. Pharmacogenetics and anaesthesia: the value of genetic profiling.

    PubMed

    Landau, R; Bollag, L A; Kraft, J C

    2012-02-01

    Approximately 50 years ago, pharmacogenetics was described as a new field of medicine that may explain human drug action. Anaesthesia played a key role in the early investigations. An understanding of how a person's DNA influences drug metabolism and effectiveness may allow individually tailored prescriptions, improving outcomes and safety. The ultimate goal of pharmacogenetic research is to offer tailored personalised medicine to improve both the efficacy of medication and patient safety by helping to predict risk of adverse outcomes. In this review, we present a selection of historical landmarks where anaesthesia has been a catalyst for pharmacogenetic development. We examine the level of evidence and cite examples of candidate genes and common polymorphisms known to alter the response to peri-operative medication. Finally, we set forth current views and potential exciting perspectives that may arise from the application of pharmacogenetics to the daily practice of anaesthesia and pain medicine. PMID:22251108

  8. [Pharmacogenetics in primary health care: implementation and future expectations].

    PubMed

    Houwink, Elisa J F; Rigter, Tessel; Swen, Jesse J; Cornel, Martina C; Kienhuis, Anne; Rodenburg, Wendy; Weda, Marjolein

    2015-01-01

    Personalised medicine is a targeted approach to the prevention, diagnosis and treatment of disorders on the basis of the specific genetic profile of the patient. Pharmacogenetics research shows that differences in the genetic profile of patients explain the interindividual differences in efficacy and side effects of medicines. Although there are high expectations of personalised medicine and pharmacogenetics in healthcare, both are only used to a limited extent to date. Pharmacogenetics seems particularly important in diseases with a poor prognosis and treatments with potentially serious side effects. Pharmacogenetics testing is reimbursed in the case of serious side effects or unexpected ineffectiveness. 95% of patients in the Netherlands have at least one abnormality in the panel of genes for which guidance is available. The KNMP (Royal Dutch Pharmacists' Association) provides dosing advice based on genotype for 80 medicines, 27 of which are regularly prescribed in primary health care. PMID:26507063

  9. Pharmacogenetics in clinical pediatrics: challenges and strategies

    PubMed Central

    Van Driest, Sara L; McGregor, Tracy L

    2013-01-01

    The use of genetic information to guide medication decisions holds great promise to improve therapeutic outcomes through increased efficacy and reduced adverse events. As in many areas of medicine, pediatric research and clinical implementation in pharmacogenetics lag behind corresponding adult discovery and clinical applications. In adults, genotype-guided clinical decision support for medications such as clopidogrel, warfarin and simvastatin are in use in some medical centers. However, research conducted in pediatric populations demonstrates that the models and practices developed in adults may be inaccurate in children, and some applications lack any pediatric research to guide clinical decisions. To account for additional factors introduced by developmental considerations in pediatric populations and provide pediatric patients with maximal benefit from genotype-guided therapy, the field will need to develop and employ creative solutions. In this article, we detail some concerns about research and clinical implementation of pharmacogenetics in pediatrics, and present potential mechanisms for addressing them. PMID:24363766

  10. Recent advances in optogenetics and pharmacogenetics.

    PubMed

    Aston-Jones, Gary; Deisseroth, Karl

    2013-05-20

    Optogenetics with microbial opsin genes, and pharmacogenetics with designer receptors, represent potent and versatile experimental modalities that can be integrated with each other as well as with a rich diversity of synergistic methods to provide fundamental opportunities in neuroscience research. The 7th Annual Brain Research Meeting in New Orleans in October 2012, Optogenetics and Pharmacogenetics in Neuronal Function and Dysfunction, brought together leading researchers that have developed and used these tools to explore a wide range of questions in nervous system function and dysfunction. This special issue of Brain Research includes articles by speakers in this meeting and others, which together synthesize and summarize the state of the art for optogenetics and designer receptors. This article is part of a Special Issue entitled Optogenetics (7th BRES).

  11. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  12. Pharmacogenetics of analgesic drugs

    PubMed Central

    Russo, Giovanna; Gubbay, Anthony; Branford, Ruth; Sato, Hiroe

    2013-01-01

    Summary points • Individual variability in pain perception and differences in the efficacy of analgesic drugs are complex phenomena and are partly genetically predetermined. • Analgesics act in various ways on the peripheral and central pain pathways and are regarded as one of the most valuable but equally dangerous groups of medications. • While pharmacokinetic properties of drugs, metabolism in particular, have been scrutinised by genotype–phenotype correlation studies, the clinical significance of inherited variants in genes governing pharmacodynamics of analgesics remains largely unexplored (apart from the µ-opioid receptor). • Lack of replication of the findings from one study to another makes meaningful personalised analgesic regime still a distant future. • This narrative review will focus on findings related to pharmacogenetics of commonly used analgesic medications and highlight authors’ views on future clinical implications of pharmacogenetics in the context of pharmacological treatment of chronic pain. PMID:26516523

  13. Linking pharmacovigilance with pharmacogenetics.

    PubMed

    Clark, David W J; Donnelly, Emma; Coulter, David M; Roberts, Rebecca L; Kennedy, Martin A

    2004-01-01

    The ability to identify individuals who are susceptible to adverse drug reactions (ADRs) has the potential to reduce the personal and population costs of drug-related morbidity. Some individuals may show an increased susceptibility to certain ADRs through genetic polymorphisms that alter their responses to various drugs. We wished to establish a methodology that would be acceptable to members of the general population and that would enable estimation of the risks that specific genetic factors confer on susceptibility to specific ADRs. Buccal swabs were selected as a minimally invasive method to obtain cells for DNA extraction. We wished to determine whether DNA of sufficient quantity and quality could be obtained to enable genotyping for two different polymorphic genes that code for enzymes that are widely involved in drug disposition. This article describes a small pilot study of methodology developed in the New Zealand Intensive Medicines Monitoring Programme (IMMP) to link prescription event monitoring (PEM) studies with pharmacogenetics. The methodology involves a nested case-control study design to investigate whether patients with genetic variants in P-glycoprotein (P-gp) and cytochrome P450 (CYP) 2C9 are more susceptible to psychiatric or visual disturbances following cyclo- oxygenase-2 inhibitor use (ADR signals identified in the IMMP database) than matched control patients taking the medication without experiencing any ADRs. It was concluded that the use of buccal swabs is acceptable to patients and provides DNA of sufficient quantity and quality for genotyping. Although no differences in the distribution of genotypes in the case and control populations were found in this small study, case-control studies investigating genetic risks for ADRs using drug cohorts from PEM studies are possible, and there are several areas where population-based studies of genetic risk factors for ADRs are needed. Examples are discussed where research in large populations is

  14. Pharmacogenetically driven treatments for alcoholism: are we there yet?

    PubMed

    Arias, Albert J; Sewell, R Andrew

    2012-06-01

    Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D(4) receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject's age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice. PMID:22587755

  15. Pharmacogenetics and outcome with antipsychotic drugs

    PubMed Central

    Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

    2014-01-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

  16. Pharmacogenetics and outcome with antipsychotic drugs.

    PubMed

    Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

    2014-12-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

  17. Challenges in pharmacogenetics.

    PubMed

    Cascorbi, Ingolf; Bruhn, Oliver; Werk, Anneke N

    2013-05-01

    The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes. This review highlights the current challenging and most promising examples of PGx. PMID:23640184

  18. A Pharmacogenetics Service Experience for Pharmacy Students, Residents, and Fellows

    PubMed Central

    Drozda, Katarzyna; Labinov, Yana; Jiang, Ruixuan; Thomas, Margaret R.; Wong, Shan S.; Patel, Shitalben; Nutescu, Edith A.

    2013-01-01

    Objective. To utilize a comprehensive, pharmacist-led warfarin pharmacogenetics service to provide pharmacy students, residents, and fellows with clinical and research experiences involving genotype-guided therapy. Design. First-year (P1) through fourth-year (P4) pharmacy students, pharmacy residents, and pharmacy fellows participated in a newly implemented warfarin pharmacogenetics service in a hospital setting. Students, residents, and fellows provided genotype-guided dosing recommendations as part of clinical care, or analyzed samples and data collected from patients on the service for research purposes. Assessment. Students’, residents’, and fellows’ achievement of learning objectives was assessed using a checklist based on established core competencies in pharmacogenetics. The mean competency score of the students, residents, and fellows who completed a clinical and/or research experience with the service was 97% ±3%. Conclusion. A comprehensive warfarin pharmacogenetics service provided unique experiential and research opportunities for pharmacy students, residents, and fellows and sufficiently addressed a number of core competencies in pharmacogenetics. PMID:24159216

  19. Rare Diseases Clinical Research Network

    MedlinePlus

    ... RDCRN? Aims of the Rare Diseases Clinical Research Network Contact Us RDCRN Members Login Accessibility Disclaimer The Rare Diseases Clinical Research Network is an initiative of the Office of Rare ...

  20. Pharmacogenetic considerations in the treatment of Alzheimer's disease.

    PubMed

    Cacabelos, Ramón; Torrellas, Clara; Teijido, Oscar; Carril, Juan Carlos

    2016-06-01

    The practical pharmacogenetics of Alzheimer's disease (AD) is circumscribed to acetylcholinesterase inhibitors (AChEIs) and memantine. However, pharmacogenetic procedures should be applied to novel strategies in AD therapeutics including: novel AChEIs and neurotransmitter regulators, anti-Aβ treatments, anti-tau treatments, pleiotropic products, epigenetic drugs and combination therapies. Genes involved in the pharmacogenetic network are under the influence of the epigenetic machinery which regulates gene expression transcriptionally and post-transcriptionally, configuring the fundamentals of pharmacoepigenomics. Over 60% of AD patients present concomitant pathologies demanding additional treatments which increase the likelihood of drug-drug interactions. Lipid metabolism dysfunction is a pathogenic mechanism inherent to AD neurodegeneration. The therapeutic response to hypolipidemic compounds is influenced by the APOE and CYP genotypes. The development of novel compounds and the use of combination/multifactorial treatments require the implantation of pharmacogenomic procedures for the avoidance of ADRs and the optimization of therapeutics. PMID:27291247

  1. Epigenetic techniques in pharmacogenetics.

    PubMed

    Heil, Sandra G

    2013-01-01

    Pharmacoepigenetics is an emerging field, which can be studied by several approaches. Addressing DNA methylation status of drug-metabolizing enzymes and transporters (DMET) is challenging and might provide answers in relation to interindividual differences in pharmacokinetics and pharmacodynamics. Studying genetic variation in DMET genes in relation to drug response has been the main focus of pharmacogenetics laboratories; it is, however, expected that epigenetic modifications will play a role in drug responses as well. Some of the variations in drug-responses cannot be explained by genetic variation in DMET genes. For those particular genes it might be interesting to examine the DNA methylation status in relation to pharmacokinetics. In this chapter we discuss the methods available and provide a protocol to quantify DNA methylation status of CpG sites in candidate genes, which can readily be applied to most pharmacogenetics laboratories. In addition, we provide details about optimization and validation of the method in terms of technical specificity and technical sensitivity and precision of the method.

  2. Pharmacogenetics of Antipsychotics

    PubMed Central

    Brandl, Eva J; Kennedy, James L; Müller, Daniel J

    2014-01-01

    Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods: We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses. Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion: First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. PMID:24881126

  3. Clinical Pharmacogenetics Implementation

    PubMed Central

    WEITZEL, KRISTIN W.; ELSEY, AMANDA R.; LANGAEE, TAIMOUR Y.; BURKLEY, BENJAMIN; NESSL, DAVID R.; OBENG, ANIWAA OWUSU; STALEY, BENJAMIN J.; DONG, HUI-JIA; ALLAN, ROBERT W.; LIU, J. FELIX; COOPER-DEHOFF, RHONDA M.; ANDERSON, R. DAVID; CONLON, MICHAEL; CLARE-SALZLER, MICHAEL J.; NELSON, DAVID R.; JOHNSON, JULIE A.

    2014-01-01

    Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist-led, multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long-term goals to include expansion to disease-risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementation. The initial clinical implementation of the UF PMP began in June 2012 and targeted clopidogrel use and the CYP2C19 genotype in patients undergoing left heart catheterization and percutaneous-coronary intervention (PCI). After 1 year, 1,097 patients undergoing left heart catheterization were genotyped preemptively, and 291 of those underwent subsequent PCI. Genotype results were reported to the medical record for 100% of genotyped patients. Eighty patients who underwent PCI had an actionable genotype, with drug therapy changes implemented in 56 individuals. Average turnaround time from blood draw to genotype result entry in the medical record was 3.5 business days. Seven different third party payors, including Medicare, reimbursed for the test during the first month of billing, with an 85% reimbursement rate for outpatient claims that were submitted in the first month. These data highlight multiple levels of success in clinical implementation of genomic medicine. PMID:24616371

  4. Pharmacogenetics and Antipsychotics: Therapeutic Efficacy and Side Effects Prediction

    PubMed Central

    Zhang, Jian-Ping; Malhotra, Anil K.

    2010-01-01

    Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences is clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one's genetic markers. Areas covered in this review This article reviews the pharmacogenetic literature from early 1990s to 2010, focusing on two aspects of drug action: pharmacokinetics and pharmacodynamics. Genetic variants in the neurotransmitter receptors including dopamine and serotonin, and metabolic pathways of drugs including CYP2D6 and COMT, were discussed in association with clinical drug response and side effects. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic research of antipsychotic drugs is both promising and challenging. There is consistent evidence that some genetic variants can affect clinical response and side effects. However, more studies that are designed specifically to test pharmacogenetic hypotheses are clearly needed to advance the field. PMID:21162693

  5. Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations

    PubMed Central

    Eum, Seenae; Lee, Adam M.; Bishop, Jeffrey R.

    2016-01-01

    Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed. PMID:27757066

  6. Pharmacogenetics of alcohol, nicotine and drug addiction treatments.

    PubMed

    Sturgess, Jessica E; George, Tony P; Kennedy, James L; Heinz, Andreas; Müller, Daniel J

    2011-07-01

    The numerous premature deaths, medical complications and socio-economic repercussions of drug and alcohol addiction suggest that improvements in treatment strategies for addictive disorders are warranted. The use of pharmacogenetics to predict response to medication, side effects and appropriate dosages is relatively new in the field of drug addiction. However, increasing our understanding of the genetic factors influencing these processes may improve the treatment of addiction in the future. We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost-effectiveness require further investigation. However, the data summarized in this review demonstrate that pharmacogenetic factors play a role in response to addiction pharmacotherapy and have the potential to aid in the personalization of addiction treatments. Such data may lead to improved cessation rates by allowing physicians to select medications for individuals based, at least in part, on genetic factors that predispose to treatment success or failure rather than on a trial and error basis. PMID:21362114

  7. Susceptibility genes and pharmacogenetics in ocular inflammatory disorders.

    PubMed

    Liu, Baoying; Sen, H Nida; Nussenblatt, Robert

    2012-10-01

    Ocular inflammatory disorders encompass uveitis, scleritis, keratitis, and other ocular diseases where inflammation may play a role. Although age-related macular degeneration (AMD) is clinically characterized by degenerative changes in the macula, accumulating evidence suggests that inflammation plays an important role in its pathogenesis. Pharmacogenetics is the study of the influence of genetic variation and its effects on drug efficacy or toxicity. There are no pharmacogenetic studies in uveitis and very few in AMD therapies. In this review, the authors describe the susceptibility genes related to uveitis and AMD and the important advances in pharmacogenetic research in relation to AMD and uveitis therapy. They propose polygenic and composite models of treatment responses to fulfill individualized drug therapy in intraocular inflammatory disorders. PMID:22974049

  8. Advances and challenges in fluoropyrimidine pharmacogenomics and pharmacogenetics.

    PubMed

    Soong, Richie; Diasio, Robert B

    2005-12-01

    In cancer pharmacogenetics (the study of how variability in a single or set of known genes influences drug response) and pharmacogenomics (the study of variability on a genome-wide scale), one of the most important fields of research focuses on the fluoropyrimdines (FPs) and, in particular, 5-fluorouracil (5-FU). After over 40 years of use, FPs remain one of the most commonly used cancer chemotherapy agents and their application includes a wide spectrum of cancer types. FPs also continue to be the baseline component for many new regimens with novel molecular-targeted agents that are being rapidly introduced. Hence, it would seem appropriate that pharmacogenetic/genomic models for optimizing cancer patient management would involve indicators of FP response. In this article, the current trends in FP pharmacogenetics and pharmacogenomics are reviewed based on the advances made to date and the challenges faced in realizing their full potential.

  9. Pharmacogenetics and personalized medicine: the future for drug prescribing.

    PubMed

    Mitri, Zahi; Esmerian, Maria O; Simaan, Joseph A; Sabra, Ramzi; Zgheib, Nathalie K

    2010-01-01

    Pharmacogenetics, the study of interindividual variations in DNA sequence related to drug response, aims at the optimization of treatment regimens based on each patient's unique genetic makeup. Currently, there is a trend towards moving away from the concept of "one drug fits all" to a rather more individualized and personalized medicine. The goal is to define the appropriate drug dose that maximizes efficacy and minimizes toxicity in each individual patient. An example of genotyping for CYP2C9 genetic polymorphisms in patients receiving oral anticoagulants is provided. In spite of its inherent challenges, we hope that pharmacogenetic research and clinical applications expand to improve healthcare outcomes in Lebanon and worldwide. PMID:20549897

  10. [Pharmacogenetics of oral antidiabetic treatment].

    PubMed

    Tkáč, Ivan

    2016-03-01

    Pharmacogenetics is the study of how genes (individual genotypes) affect a persons response to drugs. At present, recommendations made about the treatment of some monogenic forms of diabetes are based on genetic diagnostics. The first studies in the field of pharmacogenetics of oral antidiabetics have now been published which have identified associations of individual genetic variants with response to treatment. The response to sulfonylurea derivatives was significantly associated with the variants KCNJ11/ABCC8, TCF7L2 and CYP2C9. The response to metformin treatment was associated with the genetic variants ATM and SLC47A1. The response to treatment with glitazones was associated with the genetic variant PPARG. The therapeutic response to the treatment with gliptins was associated with the genetic variants TCF7L2 and CTRB1/2. It may be expected that in the near future pharmacogenetic knowledge will also be used within personalized treatment of type 2 diabetes. PMID:27180666

  11. [Pharmacogenetics. Tailored therapy in medicine -- opportunities and challenges].

    PubMed

    Scharplatz, M; Puhan, M; Steurer, J; Bachmann, L M

    2004-03-01

    This article provides a general introduction into the field of pharmacogenetics and discusses its opportunities and limits. Pharmacogenetic research explores genetic variability between patients to explain observed differences in effectiveness of a drug therapy or adverse event profiles. Sometimes drug therapy is unfavourable: Patients may respond only partially to a drug therapy, do not respond at all, or suffer from serious adverse events. The reasons for the varying effectiveness of a drug therapy are due to factors like absorption; metabolism, elimination and target interaction. Recent research has led to a better understanding of the molecular genetic mechanisms behind those factors. Numerous new polymorphisms have been described, for example for the beta 2-adrenergic receptor or the cytochrome which can either improve or reduce the response to drug therapy. Two polymorphisms for the tumour necrosis factor alpha have shown to be associated with an increased risk of serious adverse events (hypersensibility: fever, rash, gastrointestinal symptoms) if treated with abacavir (HIV-treatment). Pharmacogenetic tests provide information about certain polymorphisms and raise the hope for an individualized pharmacotherapy. Yet, not only genetic but also environmental factors influence the effectiveness of a therapy. Even though results from research implies that pharmacogenetics has a great potential to maximize the effectiveness of pharmacotherapy and to reduce the incidence of drug-related adverse events, extensive clinical research both on effectiveness and costs is required to assess the true benefits of these exciting new technologies. PMID:15052854

  12. Sarcomas and pharmacogenetics.

    PubMed

    Biason, Paola; Toffoli, Giuseppe

    2005-09-01

    Sarcomas are a heterogeneous group of tumors, requiring different chemotherapeutic approaches. Recently, several regimens for metastatic tumors were evaluated with respect to the different responses to conventional chemotherapy of the various histologic subtypes of sarcomas. The impact of pharmacogenetics in the progress of chemotherapy appears to be crucial in defining the clinical response to many drugs, such as anthracycline or alkylating agents, that are widely used in treatment regimens for soft tissue sarcomas (STS) or sarcomas of the bone. Polymorphisms of metabolizing enzymes (e.g., cytochrome P450 and glutathione-S-transferase), transporter proteins (reduced folate carrier and P-glycoprotein) or target proteins (thymidylate synthase, methylenetetrahydrofolate reductase, dihydrofolate reductase, and c-KIT) may be responsible for an altered clinical outcome, in terms of both response and toxicity. The administration of new chemotherapeutic agents, such as imatinib for gastrointestinal tumors (GIST), requires the study of genetic polymorphisms possibly affecting the integrity of the target (c-KIT), which may provide valid information regarding possible developments of therapy. For STS and sarcoma of the bone, the genetic markers, which could be unambiguously predictive of the phenotypic profile of patients, are as yet undetermined.

  13. Clinical Application of Pharmacogenetics: Where are We Now?

    PubMed Central

    2013-01-01

    Pharmacogenetic (PGx) testing has the potential to improve drug therapy in an individual by informing appropriate drug dosing or drug selection in order to maximize efficacy and safety. Although multiple studies have illustrated the potential benefits of such testing when applied to specific drugs across a broad range of therapy areas, the uptake of PGx testing in routine clinical practice has been relatively limited. Implementation appears to be hampered by the absence of sufficiently strong evidence linking the results of testing with actionable benefits in terms of clinical outcomes. Meanwhile, there are now adequate data to allow dosing recommendations as have been developed by bodies including the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) in several settings, including TPMT/thiopurines, CYP2C19/clopidogrel, CYP2D6/codeine, VKORC1-CYP2C9/warfarin, HLA-B*5701/abacavir, SLCO1B1/simvastatin and HLAB*5801/allopurinol. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) have also recently initiated surveys in order to better understand the extent of, and the role played by, PGx testing in clinical practice. This should help identify where further training and education may be beneficial. To this end, in collaboration with ESPT, the IFCC Pharmacogenetic Laboratory Network has now been formed, with the aim of improving the uptake and quality of PGx testing.

  14. Pharmacogenetics of β-Blockers

    PubMed Central

    Shin, Jaekyu; Johnson, Julie A.

    2009-01-01

    β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice. PMID:17542770

  15. [Pharmacogenetics and anxiety disorders: analysis of recent findings].

    PubMed

    Amitai, Maya; Kronenberg, Sefi; Cohen, Tali; Frisch, Amos; Weizman, Abraham; Apter, Alan

    2014-01-01

    Anxiety disorders are chronic disorders appearing with a high frequency in the general population and causing much distress to those suffering from them. The current common treatment consists of antidepressants, primarily from the serotonin-selective-reuptake-inhibitor (SSRI) class. However, despite the relative effectiveness of these medications the patients' responses vary widely with one third not responding at all. While we do not currently have the ability to predict who will respond positively to the medication, it is hoped that genetic research will make it possible to prospectively identify responders and thus help avoid failed treatment attempts and side-effects. The field of pharmacogenetics is divided into pharmaco-kinetics (genetic factors that influence the drug metabolism in the body) and pharmco-dynamics (genetic factors that affect the response to the drug at the level of the receptors/transporters/enzymes in the target organs). Contrary to the treatment of depression, there is little research available on the pharmacogenetics of anxiety disorders and the existing research coincides with the studies on depression. The primary pharmacogenetic-dynamic findings are related to serotonergic genes of which those with the long allele of the serotonin transporter gene (5-HTTLPR) are expected to respond positively to treatment, and the same is true regarding genetic variants of several serotonin receptors. The pharmacogenetic-kinetic findings focus on the CYP450 enzyme system. The hope is that with the progression of the pharmacogenetic research new genetic variants will be discovered which, when combined with the clinical characteristics of those suffering from anxiety disorders, will enable the development of novel treatment algorithms to be customized for each patient. PMID:24791568

  16. Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.

    PubMed

    Cho, Chul-Hyun; Lee, Heon-Jeong

    2013-10-01

    Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic use. Because of genetic susceptibility for developing TD and because it is difficult to predict and prevent its development prior to or during the early stages of medication, pharmacogenetic research of TD is important. Additionally, these studies enhance our knowledge of the genetic mechanisms underlying abnormal dyskinetic movements, such as Parkinson's disease. However, the pathophysiology of TD remains unclear. The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of the oxidative stress hypothesis of TD indicate that neurotoxic free radical production is likely a consequence of antipsychotic medication and is related to the occurrence of TD. Several studies on TD have focused on examining the genes involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala-9Val polymorphisms show a relatively consistent association with TD susceptibility, although not all studies support this. Numerous pharmacogenetic studies have found a positive relationship between TD and oxidative stress based on genes involved in the antioxidant defense mechanism, dopamine turnover and metabolism, and other antioxidants such as estrogen and melatonin. However, many of the positive findings have not been replicated. We expect that more research will be needed to address these issues. PMID:23123399

  17. [Network Research on Human Papillomavirus].

    PubMed

    Almeida-Gutiérrez, Eduardo; Paniagua, Ramón; Furuya, María ElenaYuriko

    2015-01-01

    In order to increase the research in important health questions at a national and institutional levels, the Human Papillomavirus Research Network of the Health Research Coordination of the Instituto Mexicano del Seguro Social offers this supplement with the purpose of assisting patients that daily look for attention due to the human papillomavirus or to cervical cancer.

  18. Pharmacogenetic variation and metformin response.

    PubMed

    Chen, Suning; Zhou, Jie; Xi, Miaomiao; Jia, Yanyan; Wong, Yan; Zhao, Jinyi; Ding, Likun; Zhang, Jian; Wen, Aidong

    2013-12-01

    Diabetes is a major health problem worldwide, and metformin, a traditional oral anti-hyperglycemic drug, is now believed to be the most widely prescribed antidiabetic drug. Metformin acts primarily by inhibiting hepatic glucose production and improving insulin sensitivity. Metformin is absorbed predominately by the small intestine and excreted in an unaltered form in the urine. The pharmacokinetics of metformin is primarily determined by membrane transporters, including the plasma membrane monoamine transporter (PMAT), the organic cation transporters (OCTs), the multidrug and toxin extrusion (MATE) transporters, and the critical protein kinase AMPactivated protein kinase (AMPK). PMAT may play a role in the uptake of metformin from the gastrointestinal tract, while OCTs mediate the intestinal absorption, hepatic uptake, and renal excretion of metformin. MATEs are believed to contribute to the hepatic and renal excretion of the drug. The pharmacologic effects of metformin are primarily exerted in the liver, at least partly via the activation of AMPK and the subsequent inhibition of gluconeogenesis. A considerable amount of pharmacogenetic research has demonstrated that genetic variation is one of the major factors affecting metformin response. Moreover, it has become increasingly clear that membrane transporters are important determinants of the pharmacokinetics of metformin. In this review, we will discuss the genetic variants of major transporters that purportedly determine the pharmacokinetics of metformin in terms of drug bioavailability, distribution, and excretion, such as PMAT, OCTs, and MATEs. Understanding how genetic variation affects metformin response will help promote more effective use of the drug for the treatment of type 2 diabetes (T2D). PMID:24329113

  19. Pharmacogenetics in type 2 diabetes: potential implications for clinical practice.

    PubMed

    Huang, Chunmei; Florez, Jose C

    2011-01-01

    Pharmacogenetic research aims to study how genetic variation may influence drug efficacy and/or toxicity; pharmacogenomics expands this quest to the entire genome. Pharmacogenetic findings may help to uncover new drug targets, illuminate pathophysiology, clarify disease heterogeneity, aid in the fine-mapping of genetic associations, and contribute to personalized treatment. In diabetes, there is precedent for the successful application of pharmacogenetic concepts to monogenic forms of the disease, such as maturity onset diabetes of the young or neonatal diabetes. Whether similar insights will be produced for the common form of type 2 diabetes remains to be seen. With recent advances in genetic approaches, the successive application of candidate gene studies, large-scale genotyping studies and genome-wide association studies has begun to generate suggestive results that may lead to changes in clinical practice. However, many potential barriers to the translation of pharmacogenetic discoveries to the clinical management of diabetes still remain. Here, we offer a contemporary overview of the field in its current state, identify potential obstacles, and highlight future directions. PMID:22126607

  20. The impact of pharmacogenetics in the treatment of allergic disease and asthma.

    PubMed

    Jones, Bridgette L

    2011-01-01

    Personalized medicine includes the application of genomic information in predicting disease and therapeutic response to ultimately individualize patient care. Pharmacogenetics is key in achieving true personalized care. However, the clinical applicability of genetic testing to "everyday medicine" is yet to be realized. This paper will discuss areas in allergic/inflammatory disease that have been impacted by pharmacogenetic research and how this application may be brought from the "bench to the bedside." PMID:22073496

  1. Characteristics of successful recruitment in prospective pediatric pharmacogenetic studies

    PubMed Central

    Saldaña, Shannon N.; Hooper, David K.; Froehlich, Tanya E.; Campbell, Kathleen M.; Prows, Cynthia A.; Sadhasivam, Senthilkumar; Nick, Todd G.; Seid, Michael; Vinks, Alexander A.; Glauser, Tracy A.

    2012-01-01

    Objective The aim was to identify factors affecting recruitment of eligible subjects in pharmacogenetic studies at a large Midwestern pediatric academic medical center. Objectives were to evaluate recruitment success of ongoing trials and ascertain contributors to differential recruitment rates. We hypothesized studies with good recruitment of eligible subjects would share characteristics not present in studies with lower than anticipated recruitment. The goal was to better understand barriers to good recruitment in pharmacogenetic studies to help inform future trial and infrastructure design. Study Design Investigators designed a survey with proposed elements of success, which was then completed by lead/site investigators of all pharmacogenetics studies at the institution. Results were evaluated using an investigator-developed likelihood of success scoring system. Results Two studies recruited over 95% of eligible patients approached, four studies were consistent with investigator-anticipated recruitment (>50%), and one study did not meet expected recruitment. A study's total score on the investigator-devised scoring tool correlated well with the proportion of approached patients recruited (Pearson correlation, r = 0.82; P<0.001). Multiple factors impact successful recruitment into these pharmacogenetic studies. Features of studies with successful recruitment included standardized clinical care, an ongoing team/patient relationship, severe/life-threatening outcome measure, study coordinator with experience in clinical research, a study medication with few or no alternative treatment options, and active involvement of the research team in clinical care. Conclusions A scoring system for study characteristics may be useful to calculate the risk of failure for successful recruitment, allow discrimination among characteristics contributing to the risk, and permit study design alterations to improve likelihood of successful recruitment in pediatric pharmacogenetic

  2. Fundamentals of Pharmacogenetics in Personalized, Precision Medicine.

    PubMed

    Valdes, Roland; Yin, DeLu Tyler

    2016-09-01

    This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between pharmacology and genetics by connecting phenotypes and genotypes in predicting the response of therapeutics in individual patients. We describe differences between precision and personalized medicine and relate principles of pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We also review basic principles of pharmacogenetics, including its evolution, how it enables the practice of personalized therapeutics, and the role of the clinical laboratory. These fundamentals are a segue for understanding specific clinical applications of pharmacogenetics described in subsequent articles in this issue.

  3. Fundamentals of Pharmacogenetics in Personalized, Precision Medicine.

    PubMed

    Valdes, Roland; Yin, DeLu Tyler

    2016-09-01

    This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between pharmacology and genetics by connecting phenotypes and genotypes in predicting the response of therapeutics in individual patients. We describe differences between precision and personalized medicine and relate principles of pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We also review basic principles of pharmacogenetics, including its evolution, how it enables the practice of personalized therapeutics, and the role of the clinical laboratory. These fundamentals are a segue for understanding specific clinical applications of pharmacogenetics described in subsequent articles in this issue. PMID:27514461

  4. Evaluating primary care research networks.

    PubMed

    Fenton, Evelyn; Harvey, Janet; Sturt, Jackie

    2007-08-01

    This paper presents a conceptual framework and tool kit, generated from the evaluation of five primary care research networks (PCRNs) funded by the then London, National Health Service (NHS) Executive. We employed qualitative methods designed to match the most important characteristics of PCRNs, conducting five contextualized case studies covering the five networks. A conceptual evaluation framework based on a review of the organization science literature was developed and comprised the broad, but inter-related organizational dimensions of structure, processes, boundaries and network self-evaluation as input factors and strategic emphasis as epitomized by network objectives. These dimensions were comprised of more detailed subdimensions designed to capture the potential of the networks to create ideas and knowledge, or intellectual capital, the key construct upon which our evaluation tool kit was based. We considered the congruence, or fit, between network objectives and input factors: greater congruence implied greater ability to achieve implicit and overt objectives. We conclude that network evaluation must take place, over time, recognizing stage of development and potential for long-term viability, but within a generic framework of inputs and outputs. If there is a good fit or congruence between their input factors and network objectives, networks will be internally coherent and able to operate at optimum effectiveness. PMID:17683655

  5. Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy.

    PubMed

    Gervasini, Guillermo; Benítez, Julio; Carrillo, Juan Antonio

    2010-08-01

    Genetic factors contribute to the phenotype of drug response, but the translation of pharmacogenetic outcomes into drug discovery, drug development or clinical practice has proved to be surprisingly disappointing. Despite significant progress in pharmacogenetic research, only a few drugs, such as cetuximab, dasatinib, maraviroc and trastuzumab, require a pharmacogenetic test before being prescribed. There are several gaps that limit the application of pharmacogenetics based upon the complex nature of the drug response itself. First, pharmacogenetic tests could be more clinically applicable if they included a comprehensive survey of variation in the human genome and took into account the multigenic nature of many phenotypes of drug disposition and response. Unfortunately, much of the existing research in this area has been hampered by limitations in study designs and the nonoptimal selection of gene variants. Secondly, although responses to drugs can be influenced by the environment, only fragmentary information is currently available on how the interplay between genetics and environment affects drug response. Third, the use of a pharmacogenetic test as a standard of care for drug therapy has to overcome significant scientific, economic, commercial, political and educational barriers, among others, in order for clinically useful information to be effectively communicated to practitioners and patients. Meanwhile, the lack of efficacy is in this process is quite as costly as drug toxicity, especially for very expensive drugs, and there is a widespread need for clinically and commercially robust pharmacogenetic testing to be applied. In this complex scenario, therapeutic drug monitoring of parent drugs and/or metabolites, alone or combined with available pharmacogenetic tests, may be an alternative or complementary approach when attempts are made to individualize dosing regimen, maximize drug efficacy and enhance drug safety with certain drugs and populations (e

  6. Pharmacogenetics and pharmacogenomics in rheumatology.

    PubMed

    Szekanecz, Zoltán; Meskó, Bertalan; Poliska, Szilard; Váncsa, Andrea; Szamosi, Szilvia; Végh, Edit; Simkovics, Enikö; Laki, Judit; Kurkó, Júlia; Besenyei, Timea; Mikecz, Katalin; Glant, Tibor T; Nagy, László

    2013-07-01

    Pharmacogenetics and pharmacogenomics deal with possible associations of a single genetic polymorphism or those of multiple gene profiles with responses to drugs. In rheumatology, genes and gene signatures may be associated with altered efficacy and/or safety of anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. In brief, genes of cytochrome P450, other enzymes involved in drug metabolism, transporters and some cytokines have been associated with responses to and toxicity of non-steroidal anti-inflammatory drugs, corticosteroids and DMARDs. The efficacy of biologics may be related to alterations in cytokine, chemokine and FcγR genes. Numerous studies reported multiple genetic signatures in association with responses to biologics; however, data are inconclusive. More, focused studies carried out in larger patient cohorts, using pre-selected genes, may be needed in order to determine the future of pharmacogenetics and pharmacogenomics as tools for personalized medicine in rheumatology.

  7. Pharmacogenetics of obesity drug therapy.

    PubMed

    Guzman, A K; Ding, M; Xie, Y; Martin, K A

    2014-01-01

    As the prevalence and severity of obesity and its complications have risen significantly in worldwide populations, behavioral interventions alone have been inconsistent in promoting sufficient, sustained weight loss. Consequently, there has been intense interest in the development of anti-obesity medications as treatment strategies. When coupled with structured lifestyle modifications, pharmacotherapy can enhance weight loss. While less efficacious than bariatric surgery, drug therapy may be an alternative to surgery for some obese patients, and is an emerging strategy for weight maintenance. The goal of pharmacogenetics is to help identify patients who will benefit most from drug therapies while minimizing the risk of adverse effects. In this review, we summarize the pharmacogenetic literature on obesity drugs of the past (sibutramine, rimonabant), present (orlistat, lorcaserin, phentermine, topiramate), and future (buprioprion/naltrexone). PMID:25109792

  8. Pharmacogenetic Treatments for Drug Addiction

    PubMed Central

    Haile, Colin N.; Kosten, Thomas R.; Kosten, Therese A.

    2009-01-01

    Background Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. Objectives To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. Methods We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. Results We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DβH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DβH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3′-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. Conclusions Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DβH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. Scientific Significance Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment. PMID:19462300

  9. Third Annual Open Meeting of the UK Pharmacogenomics and Stratified Medicine Network Conference.

    PubMed

    Bradshaw, Elizabeth H

    2015-07-01

    Third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network 14 January 2015, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK The third Annual Open Meeting of the UK Pharmacogenetics and Stratified Medicine Network was held on 14 January 2015 in association with the Wellcome Trust on the Wellcome Trust Genome Campus at Hinxton, Cambridge, UK. In the morning, speakers from Cancer Research UK, the Medical Research Council, Genomics England, Innovate UK (formerly TSB) and the Department of Health described the current major projects they are funding. In the afternoon, speakers from various universities around the United Kingdom presented data on pharmacogenetics and stratified medicine research covering diverse disease areas including cancers, warfarin dosing, Gaucher disease and rheumatoid arthritis.

  10. Pharmacogenetics of erectile dysfunction: navigating into uncharted waters.

    PubMed

    Lacchini, Riccardo; Tanus-Santos, Jose E

    2014-08-01

    Sildenafil and other PDE-5 inhibitors have revolutionized erectile dysfunction (ED) treatment. However, a significant number of patients do not respond or present adverse reactions to these drugs. While genetic polymorphisms may underlie this phenomenon, very little research has been undertaken in this research field. Most of the current knowledge is based on sildenafil, thus almost completely ignoring other important pharmacological therapies. Currently, the most promising genes with pharmacogenetic implications in ED are related to the nitric oxide and cGMP pathway, although other genes are likely to affect the responsiveness to treatment of ED. Nevertheless, the small number of studies available opens the possibility of further exploring other genes and phenotypes related to ED. This article provides a comprehensive overview of the genes being tested for their pharmacogenetic relevance in the therapy of ED.

  11. Pharmacogenetics of erectile dysfunction: navigating into uncharted waters.

    PubMed

    Lacchini, Riccardo; Tanus-Santos, Jose E

    2014-08-01

    Sildenafil and other PDE-5 inhibitors have revolutionized erectile dysfunction (ED) treatment. However, a significant number of patients do not respond or present adverse reactions to these drugs. While genetic polymorphisms may underlie this phenomenon, very little research has been undertaken in this research field. Most of the current knowledge is based on sildenafil, thus almost completely ignoring other important pharmacological therapies. Currently, the most promising genes with pharmacogenetic implications in ED are related to the nitric oxide and cGMP pathway, although other genes are likely to affect the responsiveness to treatment of ED. Nevertheless, the small number of studies available opens the possibility of further exploring other genes and phenotypes related to ED. This article provides a comprehensive overview of the genes being tested for their pharmacogenetic relevance in the therapy of ED. PMID:25303302

  12. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  13. Network Penetration Testing and Research

    NASA Technical Reports Server (NTRS)

    Murphy, Brandon F.

    2013-01-01

    This paper will focus the on research and testing done on penetrating a network for security purposes. This research will provide the IT security office new methods of attacks across and against a company's network as well as introduce them to new platforms and software that can be used to better assist with protecting against such attacks. Throughout this paper testing and research has been done on two different Linux based operating systems, for attacking and compromising a Windows based host computer. Backtrack 5 and BlackBuntu (Linux based penetration testing operating systems) are two different "attacker'' computers that will attempt to plant viruses and or NASA USRP - Internship Final Report exploits on a host Windows 7 operating system, as well as try to retrieve information from the host. On each Linux OS (Backtrack 5 and BlackBuntu) there is penetration testing software which provides the necessary tools to create exploits that can compromise a windows system as well as other operating systems. This paper will focus on two main methods of deploying exploits 1 onto a host computer in order to retrieve information from a compromised system. One method of deployment for an exploit that was tested is known as a "social engineering" exploit. This type of method requires interaction from unsuspecting user. With this user interaction, a deployed exploit may allow a malicious user to gain access to the unsuspecting user's computer as well as the network that such computer is connected to. Due to more advance security setting and antivirus protection and detection, this method is easily identified and defended against. The second method of exploit deployment is the method mainly focused upon within this paper. This method required extensive research on the best way to compromise a security enabled protected network. Once a network has been compromised, then any and all devices connected to such network has the potential to be compromised as well. With a compromised

  14. LTAR linkages with other research networks: Capitalizing on network interconnections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA ARS Research Unit based at the Jornada Experimental Range outside of Las Cruces, NM, is a member of the USDA’s Long Term Agro-ecosystem Research (LTAR) Network, the National Science Foundation’s Long Term Ecological Research (LTER) Network, the National Ecological Observation Network (NEON)...

  15. Multiple sclerosis pharmacogenetics: personalized approach towards tailored therapeutics.

    PubMed

    Grossman, Iris; Miller, Ariel

    2010-06-01

    Multiple sclerosis (MS) is a chronic autoimmune disease, where T-cells attack the myelin sheath in the central nervous system (CNS), characterized by relapsing-remitting episodes, or gradually increasing severity of symptoms and disability that accumulate over time. While current MS therapies have been proven in clinical trials to provide significant benefits, they cater only to subsets of patients. Moreover, there is an acute need to identify the most effective and safe treatment appropriate for each patient prospectively, since early intervention has been proven to prevent accumulation of irreversible dysfunction. In this review we discuss the current state-of-the-art in pharmacogenetic research as applied to the common marketed and in-development MS treatments, with respect to both efficacy and safety aspects. We conclude by discussing the relevance of pharmacogenetics and other biomarkers to the prediction, prevention and personalization of MS medications in the horizon. PMID:23199067

  16. Pharmacogenetics-based therapeutic recommendations--ready for clinical practice?

    PubMed

    Kirchheiner, Julia; Fuhr, Uwe; Brockmöller, Jürgen

    2005-08-01

    Although considerable progress has been made in basic pharmacogenetic research, less has been demonstrated in the application of pharmacogenetics (PGx)-based diagnostics to drug development and in clinical practice. There are drugs that are currently used in the clinic for which individualized therapy could be beneficial based on PGx data. However, specific, actionable recommendations on how to implement individualized therapy--particularly with respect to dosage--still have to be developed. Moreover, to apply PGx efficiently in clinical drug development, and later in drug therapy, study designs and the generation and handling of PGx data need to become more standardized. Here, we argue for the development of concise guidelines for implementation of PGx analyses in drug development and therapy.

  17. Pharmacogenetics in irritable bowel syndrome.

    PubMed

    Acosta, Andres; Camilleri, Michael

    2015-01-01

    Irritable bowel syndrome (IBS) is a chronic disease characterized by complex interactions between genetic predisposition and the environment. Current treatments for IBS are characterized by a highly variable response. Gene variations may result from insertions or deletions, gene rearrangements, splice variants or copy number variants, or, more commonly, from substitutions in the DNA of one (single nucleotide polymorphism [SNPs]) or more than one nucleotide. The objective of this editorial is to review the potential importance of pharmacogenetics in the treatment of IBS based on current evidence.

  18. Pharmacogenetic testing: current evidence of clinical utility

    PubMed Central

    Haga, Susanne B.

    2013-01-01

    Over the last decade, the number of clinical pharmacogenetic tests has steadily increased as understanding of the role of genes in drug response has grown. However, uptake of these tests has been slow, due in large part to the lack of robust evidence demonstrating clinical utility. We review the evidence behind four pharmacogenetic tests and discuss the barriers and facilitators to uptake: (1) warfarin (drug safety and efficacy); (2) clopidogrel (drug efficacy); (3) codeine (drug safety and efficacy); and (4) abacavir (drug safety). Future efforts should be directed toward addressing these issues and considering additional approaches to generating evidence basis to support clinical use of pharmacogenetic tests. PMID:24020014

  19. Pharmacogenetic challenges for the health care system.

    PubMed

    Robertson, John A; Brody, Baruch; Buchanan, Allen; Kahn, Jeffrey; McPherson, Elizabeth

    2002-01-01

    Pharmacogenetics--the effect of genotype on drug response--holds the promise of safer and more effective drug therapy. Genetic tests would be routinely given to patients prior to prescription of a drug, with therapeutic decisions based on the patient's drug-response profile. This paper examines the operational changes and the ethical, legal, and policy challenges that pharmacogenetic medicine poses for key actors in the health care system. Adaptation by drug companies, regulatory agencies, physicians, patients, insurers, and public funding agencies will be necessary to integrate pharmacogenetic medicine into health care. PMID:12117126

  20. Pharmacogenetics of smoking cessation therapy.

    PubMed

    Kortmann, Gustavo L; Dobler, Cristina J; Bizarro, Lisiane; Bau, Claiton H D

    2010-01-01

    Nicotine dependence is a major health problem, with a large amount of smoking-related premature deaths and disabilities. The dependence mechanism of nicotine is especially complex and is under strong genetic influence. Smoking cessation is associated with substantial health benefits. Evidence from animal and human studies suggests that genetic polymorphisms influencing pharmacokinetics and pharmacodynamics of nicotine may have great potential for aiding smoking treatment. There are more than 30 association studies and one genome-wide association study (GWAS) between genetic polymorphisms and smoking cessation following nicotine replacement therapy (NRT) and/or bupropion therapy. However, only a few candidate genes or regions were analyzed more than twice and even these genes require additional investigations in different therapeutic schemes. There are a growing number of new pharmacologic options that have not been pharmacogenetically assessed according to published literature. In addition, molecular genetics studies are needed to assess the functional mechanisms of some putative association results. Taken together, the preliminary findings are promising but raise the need for new studies with adequate sample sizes and adjustment for several potential confounding factors frequently neglected, such as comorbidity and sociodemographic factors. The current state of the art in the field encourages an optimist view that personalized treatment approaches may become possible. However, the current scientific evidence still does not support the use of pharmacogenetic tests in routine smoking cessation therapy. PMID:19475569

  1. Pharmacogenetics, pharmacogenomics, and individualized medicine.

    PubMed

    Ma, Qiang; Lu, Anthony Y H

    2011-06-01

    Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation. For more than 5 decades, studies of pharmacogenetics have provided ample examples of causal relations between genotypes and drug response to account for phenotypic variations of clinical importance in drug therapy. The convergence of pharmacogenetics and human genomics in recent years has dramatically accelerated the discovery of new genetic variations that potentially underlie variability in drug response, giving birth to pharmacogenomics. In addition to the rapid accumulation of knowledge on genome-disease and genome-drug interactions, there arises the hope of individualized medicine. Here we review recent progress in the understanding of genetic contributions to major individual variability in drug therapy with focus on genetic variations of drug target, drug metabolism, drug transport, disease susceptibility, and drug safety. Challenges to future pharmacogenomics and its translation into individualized medicine, drug development, and regulation are discussed. For example, knowledge on genetic determinants of disease pathogenesis and drug action, especially those of complex disease and drug response, is not always available. Relating the many gene variations from genomic sequencing to clinical phenotypes may not be straightforward. It is often very challenging to conduct large scale, prospective studies to establish causal associations between genetic variations and drug response or to evaluate the utility and cost-effectiveness of genomic medicine. Overcoming the obstacles holds promise for achieving the ultimate goal of effective and safe medication to targeted patients with appropriate genotypes.

  2. Pharmacogenetics of the β2-Adrenergic Receptor Gene

    PubMed Central

    Ortega, Victor E.; Hawkins, Gregory A.; Peters, Stephen P.; Bleecker, Eugene R.

    2009-01-01

    Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time. PMID:17996583

  3. European attitudes to gene therapy and pharmacogenetics.

    PubMed

    Hudson, John; Orviska, Marta

    2011-10-01

    Views on pharmacogenetics and gene therapy systematically differ across European countries. But despite a complex regulatory regime there is a balance of support, albeit laced with considerable uncertainty. PMID:21745587

  4. A question-based approach to adopting pharmacogenetics to understand risk for clinical variability in pharmacokinetics in early drug development.

    PubMed

    Evers, R; Blanchard, R L; Warner, A W; Cutler, D; Agrawal, N G B; Shaw, P M

    2014-09-01

    Understanding genetic variations that influence pharmacokinetics (PK) in humans is important for optimal clinical use of drugs. Guidances for making decisions on when to conduct pharmacogenetic research during drug development have been proposed by regulatory agencies, but their uniform adoption presents problems due to an inherent lack of flexibility. A questions-based approach (QBA) was developed to enable drug development teams at Merck to iteratively and flexibly evaluate the potential impact of pharmacogenetics (PGx) on clinical pharmacokinetic variability. PMID:25141952

  5. [Pharmacogenetic algorithms for predicting the appropriate dose of vitamin K antagonists: are they still useful?].

    PubMed

    Mundi, Santa; Distante, Alessandro; De Caterina, Raffaele

    2014-10-01

    The severity of side effects that may occur with vitamin K antagonists due to their narrow therapeutic window requires great attention in finding out the most appropriate dose for these drugs. Pharmacogenetic research has now considerably helped clarifying the relationships between genetic variants and sensitivity to such therapy, paving the ground to predictive algorithms that include clinical and genetic variables to establish the best doses to start and maintain an adequate anticoagulation. Pharmacogenetic algorithms indeed aim at identifying tailored regimens, reducing adverse drug reactions and subsequent hospitalizations, optimizing therapeutic efficacy and containing costs. Here we describe the results so far achieved in pharmacogenetic research with vitamin K antagonists, analyzing studies that have assessed the usefulness of such algorithms. PMID:25424019

  6. National research and education network

    NASA Technical Reports Server (NTRS)

    Villasenor, Tony

    1991-01-01

    Some goals of this network are as follows: Extend U.S. technological leadership in high performance computing and computer communications; Provide wide dissemination and application of the technologies both to the speed and the pace of innovation and to serve the national economy, national security, education, and the global environment; and Spur gains in the U.S. productivity and industrial competitiveness by making high performance computing and networking technologies an integral part of the design and production process. Strategies for achieving these goals are as follows: Support solutions to important scientific and technical challenges through a vigorous R and D effort; Reduce the uncertainties to industry for R and D and use of this technology through increased cooperation between government, industry, and universities and by the continued use of government and government funded facilities as a prototype user for early commercial HPCC products; and Support underlying research, network, and computational infrastructures on which U.S. high performance computing technology is based.

  7. Medical education practice-based research networks: Facilitating collaborative research

    PubMed Central

    Schwartz, Alan; Young, Robin; Hicks, Patricia J.; APPD LEARN, For

    2016-01-01

    Abstract Background: Research networks formalize and institutionalize multi-site collaborations by establishing an infrastructure that enables network members to participate in research, propose new studies, and exploit study data to move the field forward. Although practice-based clinical research networks are now widespread, medical education research networks are rapidly emerging. Aims: In this article, we offer a definition of the medical education practice-based research network, a brief description of networks in existence in July 2014 and their features, and a more detailed case study of the emergence and early growth of one such network, the Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network (APPD LEARN). Methods: We searched for extant networks through peer-reviewed literature and the world-wide web. Results: We identified 15 research networks in medical education founded since 2002 with membership ranging from 8 to 120 programs. Most focus on graduate medical education in primary care or emergency medicine specialties. Conclusions: We offer four recommendations for the further development and spread of medical education research networks: increasing faculty development, obtaining central resources, studying networks themselves, and developing networks of networks. PMID:25319404

  8. Research Priorities in Networking and Communications.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC.

    A workshop focused on major research issues in networking and communications. This report defines the context for research priorities and initiatives and deals with issues in networking and communications. Fifteen major research priorities and four research specific initiatives were identified by participants as areas that should be pursued over…

  9. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy

    PubMed Central

    Mei, Lin; Ontiveros, Evelena P.; Griffiths, Elizabeth A.; Thompson, James E.; Wang, Eunice S.; Wetzler, Meir

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30 years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20–40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including L-asparaginase, glucocorticoids, 6-mercaptopruine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapy. PMID:25614322

  10. Sleep Pharmacogenetics: Personalized Sleep-Wake Therapy.

    PubMed

    Holst, Sebastian C; Valomon, Amandine; Landolt, Hans-Peter

    2016-01-01

    Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations).

  11. Personalized medicine: is it a pharmacogenetic mirage?

    PubMed

    Shah, Rashmi R; Shah, Devron R

    2012-10-01

    The notion of personalized medicine has developed from the application of the discipline of pharmacogenetics to clinical medicine. Although the clinical relevance of genetically-determined inter-individual differences in pharmacokinetics is poorly understood, and the genotype-phenotype association data on clinical outcomes often inconsistent, officially approved drug labels frequently include pharmacogenetic information concerning the safety and/or efficacy of a number of drugs and refer to the availability of the pharmacogenetic test concerned. Regulatory authorities differ in their approach to these issues. Evidence emerging subsequently has generally revealed the pharmacogenetic information included in the label to be premature. Revised drugs labels, together with a flurry of other collateral activities, have raised public expectations of personalized medicine, promoted as 'the right drug at the right dose the first time.' These expectations place the prescribing physician in a dilemma and at risk of litigation, especially when evidence-based information on genotype-related dosing schedules is to all intent and purposes non-existent and guidelines, intended to improve the clinical utility of available pharmacogenetic information or tests, distance themselves from any responsibility. Lack of efficacy or an adverse drug reaction is frequently related to non-genetic factors. Phenoconversion, arising from drug interactions, poses another often neglected challenge to any potential success of personalized medicine by mimicking genetically-determined enzyme deficiency. A more realistic promotion of personalized medicine should acknowledge current limitations and emphasize that pharmacogenetic testing can only improve the likelihood of diminishing a specific toxic effect or increasing the likelihood of a beneficial effect and that application of pharmacogenetics to clinical medicine cannot adequately predict drug response in individual patients. PMID:22591598

  12. Personalized medicine: is it a pharmacogenetic mirage?

    PubMed Central

    Shah, Rashmi R; Shah, Devron R

    2012-01-01

    The notion of personalized medicine has developed from the application of the discipline of pharmacogenetics to clinical medicine. Although the clinical relevance of genetically-determined inter-individual differences in pharmacokinetics is poorly understood, and the genotype-phenotype association data on clinical outcomes often inconsistent, officially approved drug labels frequently include pharmacogenetic information concerning the safety and/or efficacy of a number of drugs and refer to the availability of the pharmacogenetic test concerned. Regulatory authorities differ in their approach to these issues. Evidence emerging subsequently has generally revealed the pharmacogenetic information included in the label to be premature. Revised drugs labels, together with a flurry of other collateral activities, have raised public expectations of personalized medicine, promoted as ‘the right drug at the right dose the first time.’ These expectations place the prescribing physician in a dilemma and at risk of litigation, especially when evidence-based information on genotype-related dosing schedules is to all intent and purposes non-existent and guidelines, intended to improve the clinical utility of available pharmacogenetic information or tests, distance themselves from any responsibility. Lack of efficacy or an adverse drug reaction is frequently related to non-genetic factors. Phenoconversion, arising from drug interactions, poses another often neglected challenge to any potential success of personalized medicine by mimicking genetically-determined enzyme deficiency. A more realistic promotion of personalized medicine should acknowledge current limitations and emphasize that pharmacogenetic testing can only improve the likelihood of diminishing a specific toxic effect or increasing the likelihood of a beneficial effect and that application of pharmacogenetics to clinical medicine cannot adequately predict drug response in individual patients. PMID:22591598

  13. Research on the model of home networking

    NASA Astrophysics Data System (ADS)

    Yun, Xiang; Feng, Xiancheng

    2007-11-01

    It is the research hotspot of current broadband network to combine voice service, data service and broadband audio-video service by IP protocol to transport various real time and mutual services to terminal users (home). Home Networking is a new kind of network and application technology which can provide various services. Home networking is called as Digital Home Network. It means that PC, home entertainment equipment, home appliances, Home wirings, security, illumination system were communicated with each other by some composing network technology, constitute a networking internal home, and connect with WAN by home gateway. It is a new network technology and application technology, and can provide many kinds of services inside home or between homes. Currently, home networking can be divided into three kinds: Information equipment, Home appliances, Communication equipment. Equipment inside home networking can exchange information with outer networking by home gateway, this information communication is bidirectional, user can get information and service which provided by public networking by using home networking internal equipment through home gateway connecting public network, meantime, also can get information and resource to control the internal equipment which provided by home networking internal equipment. Based on the general network model of home networking, there are four functional entities inside home networking: HA, HB, HC, and HD. (1) HA (Home Access) - home networking connects function entity; (2) HB (Home Bridge) Home networking bridge connects function entity; (3) HC (Home Client) - Home networking client function entity; (4) HD (Home Device) - decoder function entity. There are many physical ways to implement four function entities. Based on theses four functional entities, there are reference model of physical layer, reference model of link layer, reference model of IP layer and application reference model of high layer. In the future home network

  14. Pharmacogenetics: the bioethical problem of DNA investment banking.

    PubMed

    Corrigan, Oonagh P; Williams-Jones, Bryn

    2006-09-01

    Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development--protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or 'work', the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context. PMID:16980194

  15. The productivity of primary care research networks.

    PubMed Central

    Griffiths, F; Wild, A; Harvey, J; Fenton, E

    2000-01-01

    Primary care research networks are being publicly funded in the United Kingdom to promote a culture of research and development in primary care. This paper discusses the organisational form of these networks and how their productivity can be evaluated, drawing on evidence from management science. An evaluation of a research network has to take account of the complexity of the organisation, the influence of its local context, and its stage of development. Output measures, such as number of research papers, and process measures, such as number of research meetings, may contribute to an evaluation. However, as networking relies on the development of informal, trust-based relationships, the quality of interactions within a network is of paramount importance for its success. Networks can audit and reflect on their success in promoting such relationships and a more formal qualitative evaluation by an independent observer can document their success to those responsible for funding. PMID:11141879

  16. The productivity of primary care research networks.

    PubMed

    Griffiths, F; Wild, A; Harvey, J; Fenton, E

    2000-11-01

    Primary care research networks are being publicly funded in the United Kingdom to promote a culture of research and development in primary care. This paper discusses the organisational form of these networks and how their productivity can be evaluated, drawing on evidence from management science. An evaluation of a research network has to take account of the complexity of the organisation, the influence of its local context, and its stage of development. Output measures, such as number of research papers, and process measures, such as number of research meetings, may contribute to an evaluation. However, as networking relies on the development of informal, trust-based relationships, the quality of interactions within a network is of paramount importance for its success. Networks can audit and reflect on their success in promoting such relationships and a more formal qualitative evaluation by an independent observer can document their success to those responsible for funding. PMID:11141879

  17. Progressing the utilisation of pharmacogenetics and pharmacogenomics into clinical care.

    PubMed

    Trent, Ronald J; Cheong, Pak Leng; Chua, Eng Wee; Kennedy, Martin A

    2013-06-01

    Understanding human genetic variation and how it impacts on gene function is a major focus in genomic-based research. Translation of this knowledge into clinical care is exemplified by pharmacogenetics/pharmacogenomics. The identification of particular gene variants that might influence drug uptake, metabolism, distribution or excretion promises a more effective personalised medicine approach in choosing the right drug or its dose for any particular individual. Adverse drug responses can then be avoided or mitigated. An understanding of germline or acquired (somatic) DNA mutations can also be used to identify drugs that are more likely to be therapeutically beneficial. This represents an area of growing interest in the treatment of cancer.

  18. Pharmacogenetics in electroconvulsive therapy and adjunctive medications.

    PubMed

    Mirzakhani, Hooman; van Noorden, Martijn S; Swen, Jesse; Nozari, Ala; Guchelaar, Henk-Jan

    2015-01-01

    Electroconvulsive therapy (ECT) has shown apparent efficacy in treatment of patients with depression and other mental illnesses who do not respond to psychotropic medications or need urgent control of their symptoms. Pharmacogenetics contributes to an individual's sensitivity and response to a variety of drugs. Clinical insights into pharmacogenetics of ECT and adjunctive medications not only improves its safety and efficacy in the indicated patients, but can also lead to the identification of novel treatments in psychiatric disorders through understanding of potential molecular and biological mechanisms involved. In this review, we explore the indications of pharmacogenetics role in safety and efficacy of ECT and present the evidence for its role in patients with psychiatric disorders undergoing ECT.

  19. Pharmacogenetics of childhood acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, Elixabet; Gutierrez-Camino, Angela; Bilbao-Aldaiturriaga, Nerea; Pombar-Gomez, Maria; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2014-07-01

    Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients for which therapy fails while some patients experience severe toxicity. In the last few years, several pharmacogenetic studies have been performed to search for markers of outcome and toxicity in pediatric ALL. However, to date, TPMT is the only pharmacogenetic marker in ALL with clinical guidelines for drug dosing. In this article, we will provide an overview of the most important findings carried out in pharmacogenetics for pediatric ALL, such as the interest drawn by methotrexate transporters in the context of methotrexate treatment. Even if most of the studies are centered on coding genes, we will also point to new approaches focusing on noncoding regions and epigenetic variation that could be interesting for consideration in the near future.

  20. Pharmacogenetics of the proton pump inhibitors: a systematic review.

    PubMed

    Chong, Elaine; Ensom, Mary H H

    2003-04-01

    Cytochrome P450 (CYP) 2C19 mediates the major metabolic transformations of the proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. Genetic polymorphism of CYP2C19 can lead to significant phenotypic variation in the activity of this isoenzyme and thus in the metabolism of PPIs. We systematically reviewed the pharmacogenetic studies of PPIs with respect to the effects of CYP2C19 polymorphism on the clinical outcomes of PPI therapy. We searched MEDLINE (January 1966-August 2002) and EMBASE (January 1988-August 2002) for English-language articles on the pharmacogenetics of PPIs; the search was supplemented by a bibliographic review of all relevant articles. Seventeen pertinent citations were identified, and the quality (level) of evidence for each was categorized according to the rating scale of the United States Preventive Services Task Force. We found that the relationship between CYP2C19 genetic polymorphism and clinical outcomes after PPI therapy has not yet been clearly delineated. Virtually all pharmacogenetic studies of PPIs have been performed in Japanese men; thus, the clinical relevance of CYP2C19 genetic polymorphism in non-Asian patients and women is unknown. Differences among dual- and triple-therapy drug regimens make it difficult to compare H. pylori eradication studies and assess their applicability to current practice patterns. Drug adherence, a pivotal factor in the success of eradication therapy, was addressed in only four trials. Future directions for research include performing more studies with larger sample sizes, particularly in non-Asian populations and women; measuring plasma PPI concentrations to directly correlate H. pylori infection and ulcer cure rates with plasma drug availability; expanding the study population to patients with gastroesophageal reflux disease; and exploring the influence of CYP3A4 in the success or failure of PPI therapy. Although CYP2C19 genotyping is currently only a

  1. Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature

    PubMed Central

    Rancic, Nemanja; Dragojevic-Simic, Viktorija; Vavic, Neven; Kovacevic, Aleksandra; Segrt, Zoran; Djordjevic, Natasa

    2016-01-01

    Renal transplantation is the treatment of choice for the patients with end-stage renal failure. Genetic factors, among others, can influence variability in response to immunosuppressive drugs. Nowadays, due to restrictive health resources, the question arises whether routine pharmacogenetic analyses should be done in the renal transplant recipients or not. The aim of this literature review was to present the up-to-date information considering the economic feasibility of pharmacogenetic testing in patients subjected to renal transplantation. The organization United Network for Organ Sharing in the US estimated that total costs per renal transplant concerning these analyses were $334,300 in 2014. Pharmacogenetic testing prior to treatment initiation could be helpful to predict and assess treatment response and the risks for adverse drug reactions. This kind of testing before treatment initiation seems to be one of the most promising applications of pharmacokinetics. Although pharmacogenetic tests were found to be a cost-effective or cost-saving strategy in many cases, some authors represent another opinion. However, if the real costs of renal transplantation are recognized, the application of these tests in the standard daily practice could be considered more realistic, which additionally emphasizes the importance of future studies assessing their cost effectiveness.

  2. Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature

    PubMed Central

    Rancic, Nemanja; Dragojevic-Simic, Viktorija; Vavic, Neven; Kovacevic, Aleksandra; Segrt, Zoran; Djordjevic, Natasa

    2016-01-01

    Renal transplantation is the treatment of choice for the patients with end-stage renal failure. Genetic factors, among others, can influence variability in response to immunosuppressive drugs. Nowadays, due to restrictive health resources, the question arises whether routine pharmacogenetic analyses should be done in the renal transplant recipients or not. The aim of this literature review was to present the up-to-date information considering the economic feasibility of pharmacogenetic testing in patients subjected to renal transplantation. The organization United Network for Organ Sharing in the US estimated that total costs per renal transplant concerning these analyses were $334,300 in 2014. Pharmacogenetic testing prior to treatment initiation could be helpful to predict and assess treatment response and the risks for adverse drug reactions. This kind of testing before treatment initiation seems to be one of the most promising applications of pharmacokinetics. Although pharmacogenetic tests were found to be a cost-effective or cost-saving strategy in many cases, some authors represent another opinion. However, if the real costs of renal transplantation are recognized, the application of these tests in the standard daily practice could be considered more realistic, which additionally emphasizes the importance of future studies assessing their cost effectiveness. PMID:27630984

  3. Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature.

    PubMed

    Rancic, Nemanja; Dragojevic-Simic, Viktorija; Vavic, Neven; Kovacevic, Aleksandra; Segrt, Zoran; Djordjevic, Natasa

    2016-01-01

    Renal transplantation is the treatment of choice for the patients with end-stage renal failure. Genetic factors, among others, can influence variability in response to immunosuppressive drugs. Nowadays, due to restrictive health resources, the question arises whether routine pharmacogenetic analyses should be done in the renal transplant recipients or not. The aim of this literature review was to present the up-to-date information considering the economic feasibility of pharmacogenetic testing in patients subjected to renal transplantation. The organization United Network for Organ Sharing in the US estimated that total costs per renal transplant concerning these analyses were $334,300 in 2014. Pharmacogenetic testing prior to treatment initiation could be helpful to predict and assess treatment response and the risks for adverse drug reactions. This kind of testing before treatment initiation seems to be one of the most promising applications of pharmacokinetics. Although pharmacogenetic tests were found to be a cost-effective or cost-saving strategy in many cases, some authors represent another opinion. However, if the real costs of renal transplantation are recognized, the application of these tests in the standard daily practice could be considered more realistic, which additionally emphasizes the importance of future studies assessing their cost effectiveness. PMID:27630984

  4. LTAR Linkages with Other Research Networks: Capitalizing on Network Interconnections

    NASA Astrophysics Data System (ADS)

    Havstad, K.

    2015-12-01

    The USDA ARS Research Unit based at the Jornada Experimental Range outside of Las Cruces, NM, is a member of the USDA's Long Term Agro-ecosystem Research (LTAR) Network, the National Science Foundation's Long Term Ecological Research (LTER) Network, the National Ecological Observation Network (NEON), and the USDA's Climate Hub Network. Each of these networks has distinct functions, missions, operational characteristics, and distinct scientific and management sub-cultures (though some are fairly new and developing). Some are a fairly independent collection of research sites functioning as a network in name only, and others are truly working to develop a research synergy that could be holistic and uniquely productive. All have real scientific value, and collectively represent an investment in US research infrastructure in biology and agriculture in excess of $3B. To effectively utilize and exploit this unique research infrastructure will require a concerted effort to meld attributes of each to the benefits of their common stakeholders. Real opportunities exist to collectively utilize this infrastructure to address grand research challenges.

  5. Comprehensive Oncologic Emergencies Research Network (CONCERN)

    Cancer.gov

    The Comprehensive Oncologic Emergencies Research Network (CONCERN) was established in March 2015 with the goal to accelerate knowledge generation, synthesis and translation of oncologic emergency medicine research through multi-center collaborations.

  6. Research Networks Map | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention supports major scientific collaborations and research networks at more than 100 sites across the United States.  Five Major Programs' sites are shown on this map. | The Division of Cancer Prevention supports major scientific collaborations and research networks at more than 100 sites across the United States.

  7. A Communication Network for Educational Researchers.

    ERIC Educational Resources Information Center

    Pierce, Jean; Cooley, William W.

    1985-01-01

    Discusses application of microcomputer technology to educational research and describes the possible uses of computer networking for communication with colleagues. Focuses on the organization and structure of the Education Research Forum on CompuServe. Considers advantages and costs of networking in general and for the American Educational…

  8. Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

    PubMed

    Shuldiner, Alan R; Palmer, Kathleen; Pakyz, Ruth E; Alestock, Tameka D; Maloney, Kristin A; O'Neill, Courtney; Bhatty, Shaun; Schub, Jamie; Overby, Casey Lynnette; Horenstein, Richard B; Pollin, Toni I; Kelemen, Mark D; Beitelshees, Amber L; Robinson, Shawn W; Blitzer, Miriam G; McArdle, Patrick F; Brown, Lawrence; Jeng, Linda Jo Bone; Zhao, Richard Y; Ambulos, Nicholas; Vesely, Mark R

    2014-03-01

    Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine.

  9. Pharmacogenetics in Central American healthy volunteers: interethnic variability.

    PubMed

    Céspedes-Garro, Carolina; Naranjo, María-Eugenia G; Ramírez, Ronald; Serrano, Víctor; Fariñas, Humberto; Barrantes, Ramiro; LLerena, Adrián

    2015-03-01

    Ethnicity is one of the major factors involved in interindividual variability to drug response. This study aims to describe the frequency of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in Central American healthy volunteers and to determine its interethnic variability. Twenty-six original research articles on allelic, genotypes or metabolic phenotype frequencies were analyzed, in which a total number of 7611 Central American healthy volunteers were included (6118 were analyzed for genotype and 1799 for metabolic phenotype). No reports were available for population from Belize and Honduras. The CYP2D6*4 and *5 frequencies in Amerindian populations from Costa Rica have shown to be among the highest frequencies so far reported in the world. Furthermore, NAT2*5 and *6 presented higher frequencies in admixed populations than in Amerindians, but, inversely, the NAT2*7 was more frequent in Amerindians compared to an admixed population. Likewise, different patterns of distribution have been shown in HLA-A*02, *03 and HLA-B*07 among Native populations from Latin America. Reports on Central American populations were also found for the CYP2C19, LDLR, CYP2E1, MDR1, G6PD, TP53, CYP1A2, CYP3A4 and CYP3A5 biomarkers, but no data were available for the other 91 pharmacogenetic biomarkers revised in Central American populations. Differences in the frequency of some pharmacogenetic biomarkers and metabolic phenotypes were found, showing interethnic variability within Central American and with other Latin American populations. PMID:25490028

  10. Pharmacogenetics: Implications for Modern Type 2 Diabetes Therapy.

    PubMed

    Staiger, Harald; Schaeffeler, Elke; Schwab, Matthias; Häring, Hans-Ulrich

    2015-01-01

    Many clinical treatment studies have reported remarkable interindividual variability in the response to pharmaceutical drugs, and uncovered the existence of inadequate treatment response, non-response, and even adverse drug reactions. Pharmacogenetics addresses the impact of genetic variants on treatment outcome including side-effects. In recent years, it has also entered the field of clinical diabetes research. In modern type 2 diabetes therapy, metformin is established as first-line drug. The latest pharmaceutical developments, including incretin mimetics, dipeptidyl peptidase 4 inhibitors (gliptins), and sodium/glucose cotransporter 2 inhibitors (gliflozins), are currently experiencing a marked increase in clinical use, while the prescriptions of α-glucosidase inhibitors, sulfonylureas, meglitinides (glinides), and thiazolidinediones (glitazones) are declining, predominantly because of reported side-effects. This review summarizes the current knowledge about gene-drug interactions observed in therapy studies with the above drugs. We report drug interactions with candidate genes involved in the pharmacokinetics (e.g., drug transporters) and pharmacodynamics (drug targets and downstream signaling steps) of the drugs, with known type 2 diabetes risk genes and previously unknown genes derived from hypothesis-free approaches such as genome-wide association studies. Moreover, some new and promising candidate genes for future pharmacogenetic assessment are highlighted. Finally, we critically appraise the current state of type 2 diabetes pharmacogenetics in the light of its impact on therapeutic decisions, and we refer to major problems, and make suggestions for future efforts in this field to help improve the clinical relevance of the results, and to establish genetically determined treatment failure. PMID:27111121

  11. Collaborative knowledge in catchment research networks

    NASA Astrophysics Data System (ADS)

    Macleod, Christopher Kit

    2015-04-01

    There is a need to improve the production, sharing and use of collaborative knowledge of catchment systems through networks of researchers, policy makers and practitioners. This requires greater levels of systems based integrative research. In parallel to the growing realization that greater levels of collaborative knowledge in scientific research networks are required, a digital revolution has been taking place. This has been driven primarily by the emergence of distributed networks of computers and standards-based interoperability. The objective of this paper is to present the status and research needs for greater levels of systems based integrative research for the production, sharing and use of collaborative knowledge in catchment research networks. To enable increased levels of integrative research depends on development and application of digital technologies to improve collection, use and sharing of data and devise new knowledge infrastructures. This paper focuses on the requirements for catchment observatories that integrate existing and novel physical, social and digital networks of knowledge infrastructures. To support this focus, I present three leading international examples of collaborative networks of catchment researchers and their development of catchment observatories. In particular, the digital infrastructures they have developed to support collaborative knowledge in catchment research networks. These examples are from North America (NSF funded CUAHSI HIS) and from Europe (UK NERC funded EVOp and the German Helmholtz Association Centers funded TERENO/TEODOOR). These exemplars all supported advancing collaborative knowledge in catchment research networks through the development of catchment observatories. I will conclude by discussing the future research directions required for greater levels of production, sharing and use of collaborative knowledge in catchment research networks based on catchment systems science.

  12. Tailored therapy of ACE inhibitors in stable coronary artery disease: pharmacogenetic profiling of treatment benefit.

    PubMed

    Brugts, Jasper J; Boersma, Eric; Simoons, Maarten L

    2010-08-01

    Angiotensin-converting enzyme (ACE) inhibitors are among the most commonly used drugs in stable coronary artery disease as these agents have been proven to be effective for reducing the risk of cardiovascular morbidity and mortality. As with other drugs, individual variation in treatment benefit is likely. Such heterogeneity could be used to target ACE-inhibitor therapy to those patients most likely to benefit from treatment. However, prior attempts to target ACE-inhibitor therapy to those patients who are most likely to benefit of such prophylactic treatment in secondary prevention using clinical characteristics or the level of baseline risk appeared not to be useful. A new approach of 'tailored therapy' could be to integrate more patient-specific characteristics, such as the genetic information of patients. Pharmacogenetic research of ACE inhibitors in coronary artery disease patients is at a formative stage, and studies are limited. The Perindopril Genetic association (PERGENE) study is a large pharmacogenetic substudy of the randomized placebo-controlled European trial On Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery disease (EUROPA) trial, aimed to assess the feasibility of pharmacogenetic profiling of ACE-inhibitor therapy by perindopril. This article summarizes the recent findings of the PERGENE study and pharmacogenetic research of the treatment benefit of perindopril in stable coronary artery disease. PMID:20712529

  13. Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: some ethical and economic considerations.

    PubMed

    Morley, Katherine I; Hall, Wayne D

    2004-01-01

    Current pharmacotherapies for psychiatric disorders are generally incompletely effective. Many patients do not respond well or suffer adverse reactions to these drugs, which can result in poor patient compliance and poor treatment outcome. Adverse drug reactions and non-response are likely to be influenced by genetic polymorphisms. Pharmacogenetics holds some promise for improving the treatment of mood disorders by utilising information about genetic polymorphisms to match patients to the drug therapy that is the most effective with the fewest side effects. Pharmacogenomics promises to facilitate the development of new drugs for treatment. However, these technologies raise many ethical, economic and regulatory issues that need to be addressed before they can be integrated into psychiatry, and medicine more generally. We discuss ethical and policy issues arising from pharmacogenetic testing and pharmacogenomics research, such as informed consent, privacy and confidentiality, research on vulnerable persons and discrimination; and economic viability of pharmacogenetics and pharmacogenomics. We conclude with recommendations for the regulation and distribution of pharmacogenetic testing services and pharmacogenomic drugs.

  14. Pharmacogenetics of oral antidiabetic treatment.

    PubMed

    Schroner, Z; Javorsky, M; Kozarova, M; Tkac, I

    2011-01-01

    In the majority of patients with type 2 diabetes (T2D), oral antidiabetic drug (OAD) treatment is the first line treatment after lifestyle measures fail. Two major groups of OAD are used in clinical practice--insulin secretagogues and insulin sensitisers. Sulphonyluea (SU) derivatives are insulin secretagogues and stimulate insulin secretion by inhibiting ATP-sensitive potassium channels. Genes KCNJ11 and ABCC8 encode potassium channel proteins. KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide. In addition, the polymorphism of TCF7L2 gene, which has the strongest association with T2D, also influenced secondary SU drug failure. Insulin sensitisers include both metformin and glitazones. Some drug-genotype associations were observed for metformin in patients with T2D. Several genes influenced the effect of glitazone treatment. Rosiglitazone was more effective in diabetes control in carriers of Prol2Ala polymorphism of PPARG gene encoding the PPARg-receptor--the target of this drug. Rosiglitazone treatment had less effect on glycemic control and adiponectin increase in T2D patients with GG-genotypes of adiponectin (APM1) polymorphism. Pioglitazone treatment had smaller effect on glycemic control in patients with LPL Ser447X polymorphism. Identification of drug-genotype interactions in pharmacogenetic studies of the OAD treatment might have clinical implications in the near future resulting in selection of more specific "patient-tailored therapy" in T2D (Tab. 1, Ref. 58).

  15. Pharmacogenetics of Anti-Diabetes Drugs

    PubMed Central

    DiStefano, Johanna K.; Watanabe, Richard M.

    2010-01-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D. PMID:20936101

  16. Applicability of gene expression and systems biology to develop pharmacogenetic predictors; antipsychotic-induced extrapyramidal symptoms as an example.

    PubMed

    Mas, Sergi; Gassó, Patricia; Lafuente, Amelia

    2015-11-01

    Pharmacogenetics has been driven by a candidate gene approach. The disadvantage of this approach is that is limited by our current understanding of the mechanisms by which drugs act. Gene expression could help to elucidate the molecular signatures of antipsychotic treatments searching for dysregulated molecular pathways and the relationships between gene products, especially protein-protein interactions. To embrace the complexity of drug response, machine learning methods could help to identify gene-gene interactions and develop pharmacogenetic predictors of drug response. The present review summarizes the applicability of the topics presented here (gene expression, network analysis and gene-gene interactions) in pharmacogenetics. In order to achieve this, we present an example of identifying genetic predictors of extrapyramidal symptoms induced by antipsychotic.

  17. Research and Development Trends of Car Networking

    NASA Astrophysics Data System (ADS)

    He, Wei; Li, Zhixiong; Xie, Guotao

    With the rapid development of the world economy, road transport has become increasingly busy. An unexpected incident would cause serious traffic disaster due to traffic accidents. To solve this problem, the intelligent transportation system (ITS), which is important for the health developments of the city transportation, has become a hot topic. The car networking provides a new way for intelligent transportation system. It can ensure intelligent control and monitoring of urban road with high performance. This paper described the concept of car networking and related technology both in oversea and domestic. The importance of car networking to achieve vehicle and details of the car networking related technologies were illustrated firstly. Then, attentions focus on the research nodus of the car networking. Lastly, the development trend of car networking research was discussed.

  18. Research Networks, Mentorship and Sustainability Knowledge

    NASA Astrophysics Data System (ADS)

    Kafle, A.; Mukhopadhyay, P.; Nepal, M.; Shyamsundar, P.

    2015-12-01

    In South Asia, a majority of institutions are ill-equipped to undertake research on multi-disciplinary environmental problems, though these problems are increasing at a fast rate and connected to the region's poverty and growth objectives. In this context, the South Asian Network for Development and Environmental Economics (SANDEE) tries to fill a research, training and knowledge gap by building skills in the area of Environment and Development Economics. In this paper, the authors argue that research networks contribute to the growth of sustainability knowledge through (a) knowledge creation, (b) knowledge transfer and (c) knowledge deepening. The paper tries to show the relationship between capacity building, mentorship and research scholarship. It demonstrates that researchers, by associating with the network and its multiple training and mentoring processes, are able to build skills, change curricula and deliver useful knowledge products. The paper discusses the need for interdisciplinary research and the challenges of bridging the gap between research outputs and policy reforms.

  19. Pharmacogenetics, race, and ethnicity: social identities and individualized medical care.

    PubMed

    Foster, M W; Sharp, R R; Mulvihill, J J

    2001-06-01

    Social categories such as race and ethnicity have long been used in interpreting patient symptoms, diagnosing disease, and predicting therapeutic response. DNA-based diagnostic tests and pharmacogenetic screens could make these uses of social categories largely irrelevant by allowing clinicians to base diagnosis and treatment decisions on the unique genetic features of individual patients. Despite this attractive vision of individualized care, however, social categories are likely to continue playing a significant role in the coming era of genetic medicine. Current uses of social categories in pharmacogenetic research, for example, illustrate how drug development and marketing will perpetuate the use of social categories such as race and ethnicity. Those uses may unintentionally blunt the precision of genetic technologies and pose new threats to socially identifiable populations. These implications suggest the need for greater caution in using social categories as indicators for specific tests or therapies and for federal legislation to protect against discriminatory uses of individuals' genetic information. In addition, more precise social classifications than those presently in use may allow us to realize the full potential of DNA-based technologies, thus minimizing social disparities in health care. Those more precise social classifications should reflect extended patient pedigrees and not the self-reported claims of racial and/or ethnic affiliation.

  20. Current relevance of pharmacogenetics in immunomodulation treatment for Crohn's disease.

    PubMed

    Roberts, Rebecca L; Barclay, Murray L

    2012-10-01

    No drug therapy is completely risk free, and the costs associated with non-response and adverse effects can exceed the cost of the therapy. The ultimate goal of pharmacogenetic research is to find robust genetic predictors of drug response that enable the development of prospective genetic tests to reliably identify patients at risk of non-response or of developing an adverse effect prior to the drug being prescribed. Currently, thiopurine S-methyltransferase (TPMT) deficiency is the only pharmacogenetic factor that is prospectively assessed before azathioprine or 6-mercaptopurine immunomodulation is commenced in patients with Crohn's disease (CD). As yet no other inherited determinant of drug response has made the transition from bench to bedside for the management of this disease. In this review we summarize what is known about TPMT deficiency and explore whether there is evidence to support a role of other genetic polymorphisms in predicting the response of CD patients to thiopurine drugs, methotrexate, and anti-tumor necrosis factor α (TNFα) therapy. PMID:22741564

  1. Present status and perspective of pharmacogenetics in Mexico.

    PubMed

    Cuautle-Rodríguez, Patricia; Llerena, Adrián; Molina-Guarneros, Juan

    2014-01-01

    Drug costs account for up to 24% of the country's health expenditure and there are 13,000 registered drugs being prescribed. Diabetes is the main cause of death in the country, with over 85% of diabetic patients currently under drug treatment. The importance of knowing interindividual variability in drug metabolism on Mexican populations is thus evident. The purpose of this article is to provide an overlook of the current situation of pharmacogenetic research in Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic studies on Mexican population samples (Mestizos and Amerindian) have been published. These have reported interindividual variability through phenotyping and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT and NAT2. Some cytochromes with important clinical implications have not yet been phenotyped in Mexican populations. The development of a cocktail adapted to them could be a significant contribution to a larger knowledge on drug response variability at a lower price and shorter time. There are validated phenotyping cocktails that present several practical advantages, being valuable, safe, and inexpensive tools in drug metabolism characterization, which require only a single experiment to provide information on several cytochrome activities. PMID:24129103

  2. Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity.

    PubMed

    Di Paolo, Antonello; Bocci, Guido; Polillo, Marialuisa; Del Re, Marzia; Di Desidero, Teresa; Lastella, Marianna; Danesi, Romano

    2011-12-01

    After the rapid development of new classes of antineoplastic drugs, research activities have focused their efforts to the identification of predictive markers of drug activity and tolerability. Irinotecan (CPT-11) may induce severe toxicities (diarrhea, neutropenia) that limit its clinical use, but the increasing knowledge of its pharmacokinetics offered a potential approach to treatment optimization. Pharmacokinetics, the first area of investigation, has identified markers such as biliary index, the relative extent of conversion and the glucuronidation ratio, which are capable to define the risk for severe adverse effects. Because of the existence of some issues concerning the adoption of pharmacokinetic strategies to optimize CPT-11 dose and schedule, analyses of genetic polymorphisms seemed to offer a more reliable and safer approach for the identification of patients at risk than pharmacokinetics. In this view, the uridine diphosphate glucuronosil transferase isoform 1A1 (UGT1A1) was associated with significant changes in disposition of CPT-11 and its metabolites, and consequently with treatment-induced toxicities. However, the complex pharmacokinetics of irinotecan and the involvement of several enzymes other than UGT (i.e., carboxyl estherases, CYP450 isoforms), and transmembrane transporters (ABCB1, ABCC1, ABCG2, SLCO1B1) make difficult the identification of patients with an optimal sensitivity and specificity, and a large part of variability among patients still remains unexplained. Furthermore, prospective clinical studies that should demonstrate the reliability of those pharmacokinetic and pharmacogenetic markers are still lacking. In the present review, pharmacokinetic and pharmacogenetic markers will be discussed. PMID:21787264

  3. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review.

    PubMed

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-08-12

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  4. Present status and perspective of pharmacogenetics in Mexico.

    PubMed

    Cuautle-Rodríguez, Patricia; Llerena, Adrián; Molina-Guarneros, Juan

    2014-01-01

    Drug costs account for up to 24% of the country's health expenditure and there are 13,000 registered drugs being prescribed. Diabetes is the main cause of death in the country, with over 85% of diabetic patients currently under drug treatment. The importance of knowing interindividual variability in drug metabolism on Mexican populations is thus evident. The purpose of this article is to provide an overlook of the current situation of pharmacogenetic research in Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic studies on Mexican population samples (Mestizos and Amerindian) have been published. These have reported interindividual variability through phenotyping and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT and NAT2. Some cytochromes with important clinical implications have not yet been phenotyped in Mexican populations. The development of a cocktail adapted to them could be a significant contribution to a larger knowledge on drug response variability at a lower price and shorter time. There are validated phenotyping cocktails that present several practical advantages, being valuable, safe, and inexpensive tools in drug metabolism characterization, which require only a single experiment to provide information on several cytochrome activities.

  5. A review of pharmacogenetic studies of substance-related disorders*

    PubMed Central

    Jones, Jermaine D.; Comer, Sandra D.

    2015-01-01

    Background Substance-related disorders (SRDs) are a major cause of morbidity and mortality worldwide. Family, twin, and adoption studies have demonstrated the substantial heritability of SRDs. To determine the impact of genetic variation on risk for SRD and the response to treatment, researchers have conducted a number of secondary data analyses and quasi-experimental studies that target one or more candidate gene variants. Methods This review examines studies in which candidate polymorphisms were examined as mediator variables to identify pharmacogenetic effects on subjective responses to drug administration or cues or outcomes of medication trials for SRDs. Efforts to use a meta-analytic approach to quantify these effects are premature because the number of available studies using similar methods and outcomes is limited, so the present review is qualitative. Results Findings from these studies provide preliminary evidence of clinically relevant pharmacogenetic effects. However, independent replication of these findings has been sparse. Conclusions Although this growing body of literature has produced conflicting results, improved statistical controls may help to clarify the findings. Additionally, the use of empirically derived sub-phenotypes (i.e., which serve to differentiate distinct groups of affected individuals) may also help to identify genetic mediators of pharmacologic response in relation to SRDs. The identification of genetic mediators can inform clinical care both by identifying risk factors for SRDs and predicting adverse events and therapeutic outcomes associated with specific pharmacotherapies. PMID:25819021

  6. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

    PubMed Central

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-01-01

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  7. Network for Translational Research - Cancer Imaging Program

    Cancer.gov

    Cooperative agreement (U54) awards to establish Specialized Research Resource Centers that will participate as members of a network of inter-disciplinary, inter-institutional research teams for the purpose of supporting translational research in optical imaging and/or spectroscopy in vivo, with an emphasis on multiple modalities.

  8. Advances in neural networks research: an introduction.

    PubMed

    Kozma, Robert; Bressler, Steven; Perlovsky, Leonid; Venayagamoorthy, Ganesh Kumar

    2009-01-01

    The present Special Issue "Advances in Neural Networks Research: IJCNN2009" provides a state-of-art overview of the field of neural networks. It includes 39 papers from selected areas of the 2009 International Joint Conference on Neural Networks (IJCNN2009). IJCNN2009 took place on June 14-19, 2009 in Atlanta, Georgia, USA, and it represents an exemplary collaboration between the International Neural Networks Society and the IEEE Computational Intelligence Society. Topics in this issue include neuroscience and cognitive science, computational intelligence and machine learning, hybrid techniques, nonlinear dynamics and chaos, various soft computing technologies, intelligent signal processing and pattern recognition, bioinformatics and biomedicine, and engineering applications. PMID:19632811

  9. Advances in neural networks research: an introduction.

    PubMed

    Kozma, Robert; Bressler, Steven; Perlovsky, Leonid; Venayagamoorthy, Ganesh Kumar

    2009-01-01

    The present Special Issue "Advances in Neural Networks Research: IJCNN2009" provides a state-of-art overview of the field of neural networks. It includes 39 papers from selected areas of the 2009 International Joint Conference on Neural Networks (IJCNN2009). IJCNN2009 took place on June 14-19, 2009 in Atlanta, Georgia, USA, and it represents an exemplary collaboration between the International Neural Networks Society and the IEEE Computational Intelligence Society. Topics in this issue include neuroscience and cognitive science, computational intelligence and machine learning, hybrid techniques, nonlinear dynamics and chaos, various soft computing technologies, intelligent signal processing and pattern recognition, bioinformatics and biomedicine, and engineering applications.

  10. Physicians' opinions following pharmacogenetic testing for psychotropic medication.

    PubMed

    Walden, Lucas M; Brandl, Eva J; Changasi, Amtul; Sturgess, Jessica E; Soibel, Alexander; Notario, Janna Fe D; Cheema, Sheraz; Braganza, Nicole; Marshe, Victoria S; Freeman, Natalie; Tiwari, Arun K; Kennedy, James L; Müller, Daniel J

    2015-10-30

    Pharmacogenetics seeks to improve patient drug response and decrease side effects by personalizing prescriptions using genetic information. Since 2012, by one estimate, the number of patients who have had pharmacogenetic testing has doubled and this number is expected to double again by 2015. Given the increasing evidence for genetic influences on treatment response, we deemed it important to study physicians' opinions of pharmacogenetic testing. Surveys were completed by 168 Canadian physicians who had ordered at least one pharmacogenetic test (in particular for CYP2D6 or CYP2C19) for the prescription of psychiatric medication. Our results indicated that 80% of respondents believe genetic testing would become common standard in psychiatric drug treatment and 76% of respondents reported satisfactory or higher than satisfactory understanding of the pharmacogenetic report provided. Significantly more male physicians believed they had a higher understanding of the pharmacogenetic report compared to female physicians. To our knowledge, this is the only study that has assessed physicians' opinions of pharmacogenetic testing for psychotropic medication after they had received a pharmacogenetic report. Our results demonstrate a positive opinion of physicians on pharmacogenetics and indicate great potential for future clinical application. PMID:26298505

  11. A proposed international watershed research network

    USGS Publications Warehouse

    Osterkamp, W.R.; Gray, J.R.

    2003-01-01

    An “International Watershed Research Network” is to be an initial project of the Sino-U. S. Centers for Soil and Water Conservation and Environmental Protection. The Network will provide a fundamental database for research personnel of the Centers, as well as of the global research community, and is viewed as an important resource for their successful operation. Efforts are under way to (a) identify and select candidate watersheds, (b) develop standards and protocols for data collection and dissemination, and (c) specify other data sources on erosion, sediment transport, hydrology, and ancillary information of probable interest and use to participants of the Centers. The initial focus of the Network will be on water-deficient areas. Candidate watersheds for the Network are yet to be determined although likely selections include the Ansai Research Station, northern China, and the Walnut Gulch Experimental Watershed, Arizona, USA. The Network is to be patterned after the Vigil Network, an open-ended group of global sites and small drainage basins for which Internet-accessible geomorphic, hydrologic, and biological data are periodically collected or updated. Some types of data, using similar instruments and observation methods, will be collected at all watersheds selected for the Network. Other data from the watersheds that may reflect individual watershed characteristics and research objectives will be collected as well.

  12. Creatiing a Collaborative Research Network for Scientists

    NASA Astrophysics Data System (ADS)

    Gunn, W.

    2012-12-01

    This abstract proposes a discussion of how professional science communication and scientific cooperation can become more efficient through the use of modern social network technology, using the example of Mendeley. Mendeley is a research workflow and collaboration tool which crowdsources real-time research trend information and semantic annotations of research papers in a central data store, thereby creating a "social research network" that is emergent from the research data added to the platform. We describe how Mendeley's model can overcome barriers for collaboration by turning research papers into social objects, making academic data publicly available via an open API, and promoting more efficient collaboration. Central to the success of Mendeley has been the creation of a tool that works for the researcher without the requirement of being part of an explicit social network. Mendeley automatically extracts metadata from research papers, and allows a researcher to annotate, tag and organize their research collection. The tool integrates with the paper writing workflow and provides advanced collaboration options, thus significantly improving researchers' productivity. By anonymously aggregating usage data, Mendeley enables the emergence of social metrics and real-time usage stats on top of the articles' abstract metadata. In this way a social network of collaborators, and people genuinely interested in content, emerges. By building this research network around the article as the social object, a social layer of direct relevance to academia emerges. As science, particularly Earth sciences with their large shared resources, become more and more global, the management and coordination of research is more and more dependent on technology to support these distributed collaborations.

  13. Biological and Environmental Research Network Requirements

    SciTech Connect

    Balaji, V.; Boden, Tom; Cowley, Dave; Dart, Eli; Dattoria, Vince; Desai, Narayan; Egan, Rob; Foster, Ian; Goldstone, Robin; Gregurick, Susan; Houghton, John; Izaurralde, Cesar; Johnston, Bill; Joseph, Renu; Kleese-van Dam, Kerstin; Lipton, Mary; Monga, Inder; Pritchard, Matt; Rotman, Lauren; Strand, Gary; Stuart, Cory; Tatusova, Tatiana; Tierney, Brian; Thomas, Brian; Williams, Dean N.; Zurawski, Jason

    2013-09-01

    The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the U.S. Department of Energy (DOE) Office of Science (SC), the single largest supporter of basic research in the physical sciences in the United States. In support of SC programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet be a highly successful enabler of scientific discovery for over 25 years. In November 2012, ESnet and the Office of Biological and Environmental Research (BER) of the DOE SC organized a review to characterize the networking requirements of the programs funded by the BER program office. Several key findings resulted from the review. Among them: 1) The scale of data sets available to science collaborations continues to increase exponentially. This has broad impact, both on the network and on the computational and storage systems connected to the network. 2) Many science collaborations require assistance to cope with the systems and network engineering challenges inherent in managing the rapid growth in data scale. 3) Several science domains operate distributed facilities that rely on high-performance networking for success. Key examples illustrated in this report include the Earth System Grid Federation (ESGF) and the Systems Biology Knowledgebase (KBase). This report expands on these points, and addresses others as well. The report contains a findings section as well as the text of the case studies discussed at the review.

  14. Clinical research: a globalized network.

    PubMed

    Richter, Trevor A

    2014-01-01

    Clinical research has become increasingly globalized, but the extent of globalization has not been assessed. To describe the globalization of clinical research, we used all (n = 13,208) multinational trials registered at ClinicalTrials.gov to analyzed geographic connections among individual countries. Our findings indicate that 95% (n = 185) of all countries worldwide have participated in multinational clinical research. Growth in the globalization of clinical research peaked in 2009, suggesting that the global infrastructure that supports clinical research might have reached its maximum capacity. Growth in the globalization of clinical research is attributable to increased involvement of non-traditional markets, particularly in South America and Asia. Nevertheless, Europe is the most highly interconnected geographic region (60.64% of global connections), and collectively, Europe, North America, and Asia comprise more than 85% of all global connections. Therefore, while the expansion of clinical trials into non-traditional markets has increased over the last 20 years and connects countries across the globe, traditional markets still dominate multinational clinical research, which appears to have reached a maximum global capacity.

  15. Advanced Scientific Computing Research Network Requirements

    SciTech Connect

    Bacon, Charles; Bell, Greg; Canon, Shane; Dart, Eli; Dattoria, Vince; Goodwin, Dave; Lee, Jason; Hicks, Susan; Holohan, Ed; Klasky, Scott; Lauzon, Carolyn; Rogers, Jim; Shipman, Galen; Skinner, David; Tierney, Brian

    2013-03-08

    The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the U.S. Department of Energy (DOE) Office of Science (SC), the single largest supporter of basic research in the physical sciences in the United States. In support of SC programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet to be a highly successful enabler of scientific discovery for over 25 years. In October 2012, ESnet and the Office of Advanced Scientific Computing Research (ASCR) of the DOE SC organized a review to characterize the networking requirements of the programs funded by the ASCR program office. The requirements identified at the review are summarized in the Findings section, and are described in more detail in the body of the report.

  16. Neonatal networks: clinical research and quality improvement.

    PubMed

    Profit, Jochen; Soll, Roger F

    2015-12-01

    Worldwide, neonatal networks have been formed to address both the research and quality improvement agenda of neonatal-perinatal medicine. Neonatal research networks have led the way in conducting many of the most important clinical trials of the last 25 years, including studies of cooling for hypoxic-ischemic encephalopathy, delivery room management with less invasive support, and oxygen saturation targeting. As we move into the future, increasing numbers of these networks are tackling quality improvement initiatives as a priority of their collaboration. Neonatal quality improvement networks have been in the forefront of the quality movement in medicine and, in the 21st century, have contributed to many of the reported improvements in care. In the coming years, building and maintaining this community of care is critical to the success of neonatal-perinatal medicine.

  17. Pharmacogenetics and the Immunogenicity of Protein Therapeutics.

    PubMed

    Pandey, Gouri S; Sauna, Zuben E

    2014-12-01

    The recognition that genetic factors influence the heterogeneity of individual responses to medications with respect to both toxicity and efficacy is not new. However, only following dramatic advances in functional genomics during the last decade did the development of so-called personalized medicine become a realistic possibility. Although drug development approaches that integrate pharmacogenetic information about both the protein drug and its protein target appear logical, given the complexity of biological systems, the selection of appropriate biomarkers and the study design remain daunting tasks. Here we present potential applications of pharmacogenetics in the development of recombinant coagulation factors. In addition, we highlight the potential utility of a personalized approach to predicting and eventually circumventing immunogenicity using the recombinant Factor VIII in the treatment of hemophilia A as a model system. The immunogenicity of protein therapeutics is of increasing concern during the development and licensure of biologics and clearly calls for a pharmacogenetic approach. This is because, with immunogenicity, the predicament is not that all patients develop inhibitory antibodies but that some individuals, ethnicities, or other subpopulations have a stronger immunogenic reaction than others do.

  18. Considerations for safety pharmacogenetics in clinical practice.

    PubMed

    Frueh, Felix W

    2011-10-01

    The focus of treating an individual patient is the identification of the individual's specific needs. The measurement of the patient's characteristics, such as blood pressure or body temperature, and also the measurement of biomarkers, such as cholesterol or hemoglobin A1C is part of the patient's health assessment. The deeper the insights into the phenotypic and molecular characteristics of the patient, the better we are positioned to treat a patient. Increasingly, this assessment includes testing for certain pharmacologically relevant genetic variations (pharmacogenetics). Evaluating how the patient's genetic makeup combined with the patient's exposure to environmental influences could impact disease and treatment decisions is becoming the cornerstone of personalized medicine. However, we often use such assessments for finding the most 'effective' treatment, but we might not always be as rigorous in our assessment of potential safety risks. This is particularly apparent when looking at how safety risks are communicated. Often this information is only available as general, population-based statements and a small amount of information is available to evaluate whether or not an individual patient is at risk. Although pharmacogenetic tests that can help to assess whether an individual patient's personal risk exist (safety pharmacogenetics), they are not always performed. PMID:21888988

  19. The contribution of pharmacogenetics to pharmacovigilance.

    PubMed

    Bondon-Guitton, Emmanuelle; Despas, Fabien; Becquemont, Laurent

    2016-04-01

    Since the beginning of this century, information on pharmacogenetics appears in the summary of product characteristics (SPC) of drugs. Pharmacogenetic tests particularly concern the enzymes involved in the metabolism of drugs, among which P450 cytochromes. Some patients known as poor metabolisers eliminate some drugs more slowly, causing overdoses and adverse drug reactions (ADRs). The best-known examples are AVK and VKORC1-CYP2C9 or clopidogrel and CYP2C19. In the USA, the tests are recommended before the introduction of these drugs to prevent the occurrence of ADRs. Other tests are also commonly performed to address the toxicity of certain anticancer drugs (DPYD-capecitabine, UGT1A1-irinotecan, TPMT 6-mercaptopurine). Pharmacogenetic testing is also available to identify HLA loci that are very strongly associated with the occurrence of immuno-allergic reactions to a specific drug. The best-known example is HLA-B*5701, strongly associated with hypersensitivity to abacavir, and this test is now always prescribed before the instatement of this drug. PMID:27080842

  20. From pharmacogenetics and ecogenetics to pharmacogenomics.

    PubMed

    Motulsky, Arno G; Motuslky, Arno G

    2002-01-01

    The origin and development of pharmacogenetics are traced with emphasis on early hints by Garrod, Haldane, and later by RJ Williams. The field was delineated by Motulsky in 1957 and described as pharmacogenetics by Vogel in 1959. Kalow's monograph (1962) definitely established the discipline. Resemblance of identical twins in drug metabolism as compared with non identical twins (Vesell, 1970's) established the general importance of polygenic inheritance in disposal of many drugs. Ecogenetics was defined by Brewer in 1971 as dealing with genetic variation affecting the response to any environmental agents with emphasis on xenobiotics. More recent developments have broadened pharmacogenetic approaches to include novel genomic techniques with introduction of the term pharmacogenomics in the 1990's. Genetic and genomic approaches (toxicogenetics and toxicogenomics) are also being applied in the "environmental genome project". The interaction of genetic variation with dietary factors led to the field of Nutritional ecogenetics (Nutrigenomics) which relates the role of genetics to nutritional requirements and nutrition-mediated susceptibility to chronic disease. The total promise of pharmacogenomics is often overstated. The field is likely to have an impact on choice of drug therapy and avoidance of adverse events but is unlikely to lead to a revolution in therapeutics. Aspects of pharmacogenomic approaches and its applications including problems of premature commercialization are discussed.

  1. The contribution of pharmacogenetics to pharmacovigilance.

    PubMed

    Bondon-Guitton, Emmanuelle; Despas, Fabien; Becquemont, Laurent

    2016-04-01

    Since the beginning of this century, information on pharmacogenetics appears in the summary of product characteristics (SPC) of drugs. Pharmacogenetic tests particularly concern the enzymes involved in the metabolism of drugs, among which P450 cytochromes. Some patients known as poor metabolisers eliminate some drugs more slowly, causing overdoses and adverse drug reactions (ADRs). The best-known examples are AVK and VKORC1-CYP2C9 or clopidogrel and CYP2C19. In the USA, the tests are recommended before the introduction of these drugs to prevent the occurrence of ADRs. Other tests are also commonly performed to address the toxicity of certain anticancer drugs (DPYD-capecitabine, UGT1A1-irinotecan, TPMT 6-mercaptopurine). Pharmacogenetic testing is also available to identify HLA loci that are very strongly associated with the occurrence of immuno-allergic reactions to a specific drug. The best-known example is HLA-B*5701, strongly associated with hypersensitivity to abacavir, and this test is now always prescribed before the instatement of this drug.

  2. Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database

    PubMed Central

    Liu, Rong; Li, Xi; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Objective Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort. Methods MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling. Results BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84–8.96 mg/week, mean percentage within 20%: 45.88%–46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05). In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly

  3. Creating a national home visiting research network.

    PubMed

    Duggan, Anne; Minkovitz, Cynthia S; Chaffin, Mark; Korfmacher, Jon; Brooks-Gunn, Jeanne; Crowne, Sarah; Filene, Jill; Gonsalves, Kay; Landsverk, John; Harwood, Robin

    2013-11-01

    Home visiting can play a key role in the early childhood system of services. For home visiting to achieve its potential, decision-makers must make informed choices regarding adoption, adaptation, coordination, scale-up, and sustainment. We need a coordinated, focused, and theory-based home visiting research infrastructure to inform such decisions. The transdisciplinary Home Visiting Research Network (HVRN) was established in July 2012 with funding from the Health Resources and Services Administration. Its goal is to promote the translation of research findings into policy and practice. Its objectives are to (1) develop a national home visiting research agenda, (2) advance the use of innovative research methods; and (3) provide a research environment that is supportive of the professional development of emerging researchers interested in home visiting. A Management Team designs and directs activities to achieve these objectives through Work Teams. A Steering Committee of national leaders representing stakeholder groups oversees progress. HVRN's Coordinating Center supports the Work Teams and HVRN's Home visiting Applied Research Collaborative, a practice-based research network of home visiting programs. This article describes HVRN's rationale, approach, and anticipated products. We use home visiting-primary care coordination as an illustration, noting potential roles for pediatric practices and pediatric researchers and research educators in HVRN activities. HVRN creates the infrastructure for a rigorous program of research to inform policy and practice on home visiting as part of the system of services to improve family functioning, parenting, and child outcomes.

  4. Creating a national home visiting research network.

    PubMed

    Duggan, Anne; Minkovitz, Cynthia S; Chaffin, Mark; Korfmacher, Jon; Brooks-Gunn, Jeanne; Crowne, Sarah; Filene, Jill; Gonsalves, Kay; Landsverk, John; Harwood, Robin

    2013-11-01

    Home visiting can play a key role in the early childhood system of services. For home visiting to achieve its potential, decision-makers must make informed choices regarding adoption, adaptation, coordination, scale-up, and sustainment. We need a coordinated, focused, and theory-based home visiting research infrastructure to inform such decisions. The transdisciplinary Home Visiting Research Network (HVRN) was established in July 2012 with funding from the Health Resources and Services Administration. Its goal is to promote the translation of research findings into policy and practice. Its objectives are to (1) develop a national home visiting research agenda, (2) advance the use of innovative research methods; and (3) provide a research environment that is supportive of the professional development of emerging researchers interested in home visiting. A Management Team designs and directs activities to achieve these objectives through Work Teams. A Steering Committee of national leaders representing stakeholder groups oversees progress. HVRN's Coordinating Center supports the Work Teams and HVRN's Home visiting Applied Research Collaborative, a practice-based research network of home visiting programs. This article describes HVRN's rationale, approach, and anticipated products. We use home visiting-primary care coordination as an illustration, noting potential roles for pediatric practices and pediatric researchers and research educators in HVRN activities. HVRN creates the infrastructure for a rigorous program of research to inform policy and practice on home visiting as part of the system of services to improve family functioning, parenting, and child outcomes. PMID:24187127

  5. Clinical application of pharmacogenetics: focusing on practical issues.

    PubMed

    Chang, Matthew T; McCarthy, Jeanette J; Shin, Jaekyu

    2015-01-01

    Recent large-scale genetic-based studies have transformed the field of pharmacogenetics to identify, characterize and leverage genetic information to inform patient care. Genetic testing can be used to alter drug selection, optimize drug dosing and prevent unnecessary adverse events. As precision medicine becomes the mainstay in the clinic, it becomes critical for clinicians to utilize pharmacogenetics to guide patient care. One primary challenge is identifying patients where genetic tests that can potentially impact patient care. To address this challenge, our review highlights many practical issues clinicians may encounter: identifying candidate patients and clinical laboratories for pharmacogenetic testing, selecting highly curated resources to help asses test validity, reimbursing costs of pharmacogenetic tests, and interpreting of pharmacogenetic test results.

  6. [Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms].

    PubMed

    Kirnichnaya, K A; Sosin, D N; Ivanov, M V; Mikhaylov, V A; Ivashchenko, D V; Ershov, E E; Taraskina, A E; Nasyrova, R F; Krupitsky, E M

    2015-01-01

    "Typical" antipsychotics remain the wide-prescribed drugs in modern psychiatry. But these drugs are associated with development of extrapyramidal symptoms (EPS). Preventive methods of EPS are actively developed and they concentrate on personalized approach. The method of taking into account genetic characteristics of patient for prescribing of treatment was proven as effective in cardiology, oncology, HIV-medicine. In this review the modern state of pharmacogenetic research of antipsychotic-induced EPS are considered. There are pharmacokinetic and pharmacodynamic factors which impact on adverse effects. Pharmacokinetic factors are the most well-studied to date, these include genetic polymorphisms of genes of cytochrome P450. However, evidence base while does not allow to do the significant prognosis of development of EPS based on genetic testing of CYP2D6 and CYP7A2 polymorphisms. Genes of pharmacodynamics factors, which realize the EPS during antipsychotic treatment, are the wide field for research. In separate part of review research of such systems as dopaminergic, serotonergic, adrenergic, glutamatergic, GABAergic, BDNF were analyzed. The role of oxidative stress factors in the pathogenesis of antipsychotic-induced EPS was enough detailed considered. The system of those factors may be used for personalized risk assessment of antipsychotics' safety in the future. Although there were numerous studies, the pharmacogenetic-based prevention of EPS before prescribing of antipsychotics was not introduced. However, it is possible to distinguish the most perspectives markers for further research. Furthermore, brief review of new candidate genes provides here, but only preliminary results were published. The main problem of the field is the lack of high- quality studies. Moreover, the several results were not replicated in repeat studies. The pharmacogenetic-based research must be standardized by ethnicity of patients. But there is the ethnical misbalance in world

  7. The future of pharmacogenetics in the treatment of heart failure.

    PubMed

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C

    2015-11-01

    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome. PMID:26555119

  8. The future of pharmacogenetics in the treatment of heart failure.

    PubMed

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C

    2015-11-01

    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome.

  9. [The German research network for mental disorders].

    PubMed

    Bauer, M; Banaschewski, T; Heinz, A; Kamp-Becker, I; Meyer-Lindenberg, A; Padberg, F; Rapp, M A; Rupprecht, R; Schneider, F; Schulze, T G; Wittchen, H-U

    2016-09-01

    Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained

  10. Registers for Networked Medical Research in Germany

    PubMed Central

    Stausberg, J.; Altmann, U.; Antony, G.; Drepper, J.; Sax, U.; Schütt, A.

    2010-01-01

    Background Several disease specific registers are operated by members of the ‘TMF – Technology, Methods, and Infrastructure for Networked Medical Research’, an umbrella organization of research networks in Germany. Objective To describe the coverage and the current state as well as financial and organizational issues of registers operated by member networks of the TMF, to identify their requirements and needs, and to recommend best practice models. Methods A survey with a self-completion questionnaire including all 55 TMF member networks was carried out in winter 2007/2008. Interviews focusing on technological issues were conducted and analyzed in summer 2009 with a convenience sample of 10 registers. Results From 55 TMF member networks, 11 provided information about 14 registers. Six registers address diseases of the circulatory system with more than 150,000 registered patients. The interviews revealed a typical setting of “research registers”. Research registers are an important mean to generate hypotheses for clinical research, to identify eligible patients, and to share data with clinical trials. Concerning technical solutions, we found a remarkable heterogeneity. The analysis of the most efficient registers revealed a structure with five levels as best practice model of register management: executive, operations, IT-management, software, hardware. Conclusion In the last ten years, the TMF member networks established disease specific registers in Germany mainly to support clinical research. The heterogeneity of organizational and technical solutions as well as deficits in register planning motivated the development of respective recommendations. The TMF will continue to assist the registers in quality improvement. PMID:23616850

  11. [Cooperative Cardiovascular Disease Research Network (RECAVA)].

    PubMed

    García-Dorado, David; Castro-Beiras, Alfonso; Díez, Javier; Gabriel, Rafael; Gimeno-Blanes, Juan R; Ortiz de Landázuri, Manuel; Sánchez, Pedro L; Fernández-Avilés, Francisco

    2008-01-01

    Today, cardiovascular disease is the principal cause of death and hospitalization in Spain, and accounts for an annual healthcare budget of more than 4000 million euros. Consequently, early diagnosis, effective prevention, and the optimum treatment of cardiovascular disease present a significant social and healthcare challenge for the country. In this context, combining all available resources to increase the efficacy and healthcare benefits of scientific research is a priority. This rationale prompted the establishment of the Spanish Cooperative Cardiovascular Disease Research Network, or RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares), 5 years ago. Since its foundation, RECAVA's activities have focused on achieving four objectives: a) to facilitate contacts between basic, clinical and epidemiological researchers; b) to promote the shared use of advanced technological facilities; c) to apply research results to clinical practice, and d) to train a new generation of translational cardiovascular researchers in Spain. At present, RECAVA consists of 41 research groups and seven shared technological facilities. RECAVA's research strategy is based on a scientific design matrix centered on the most important cardiovascular processes. The level of RECAVA's research activity is reflected in the fact that 28 co-authored articles were published in international journals during the first six months of 2007, with each involving contributions from at least two groups in the network. Finally, RECAVA also participates in the work of the Spanish National Center for Cardiovascular Research, or CNIC (Centro Nacional de Investigación Cardiovascular), and some established Biomedical Research Network Centers, or CIBER (Centros de Investigación Biomédica en RED), with the aim of consolidating the development of a dynamic multidisciplinary research framework that is capable of meeting the growing challenge that cardiovascular disease will present

  12. Exploring Practice-Research Networks for Critical Professional Learning

    ERIC Educational Resources Information Center

    Appleby, Yvon; Hillier, Yvonne

    2012-01-01

    This paper discusses the contribution that practice-research networks can make to support critical professional development in the Learning and Skills sector in England. By practice-research networks we mean groups or networks which maintain a connection between research and professional practice. These networks stem from the philosophy of…

  13. Differential network analysis in human cancer research.

    PubMed

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2014-01-01

    A complex disease like cancer is hardly caused by one gene or one protein singly. It is usually caused by the perturbation of the network formed by several genes or proteins. In the last decade several research teams have attempted to construct interaction maps of genes and proteins either experimentally or reverse engineer interaction maps using computational techniques. These networks were usually created under a certain condition such as an environmental condition, a particular disease, or a specific tissue type. Lately, however, there has been greater emphasis on finding the differential structure of the existing network topology under a novel condition or disease status to elucidate the perturbation in a biological system. In this review/tutorial article we briefly mention some of the research done in this area; we mainly illustrate the computational/statistical methods developed by our team in recent years for differential network analysis using publicly available gene expression data collected from a well known cancer study. This data includes a group of patients with acute lymphoblastic leukemia and a group with acute myeloid leukemia. In particular, we describe the statistical tests to detect the change in the network topology based on connectivity scores which measure the association or interaction between pairs of genes. The tests under various scores are applied to this data set to perform a differential network analysis on gene expression for human leukemia. We believe that, in the future, differential network analysis will be a standard way to view the changes in gene expression and protein expression data globally and these types of tests could be useful in analyzing the complex differential signatures.

  14. [Cancer pharmacogenetics: study of genetically determined variations on cancer susceptibility due to xenobiotic exposure].

    PubMed

    Quiñones, Luis; Lee, Kuen; Varela F, Nelson; Escala, Mario; García, Karen; Godoy, Loreto; Castro, Andrés; Soto, Jorge; Saavedra, Iván; Cáceres, Dante

    2006-04-01

    Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components.

  15. On the use of pharmacogenetics in cancer treatment and clinical trials.

    PubMed

    Robert, Jacques; Le Morvan, Valérie; Giovannetti, Elisa; Peters, Godefridus J

    2014-10-01

    There are an increasing number of studies devoted to the identification of associations between anticancer drug efficacy and toxicity and common polymorphisms present in the patients' genome. However, many articles presenting the results of such studies do not bring the simple and necessary background information allowing the evaluation of the relevance of the study, its significance and its potential importance for patients' treatment. This position paper first addresses clinical oncologists with the aim of giving them the basic knowledge on pharmacogenetics and on the potential use of gene polymorphisms as predictive biomarkers in routine and clinical research. A secondary objective is to give molecular biologists some recommendations on how to conceive protocols and how to publish their results when they develop pharmacogenetic studies appended to clinical trials or with autonomous goals.

  16. Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    PubMed

    Campbell, Jared M; Bateman, Emma; Peters, Micah Dj; Bowen, Joanne M; Keefe, Dorothy M; Stephenson, Matthew D

    2016-03-01

    Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.

  17. Conceptualizing and Advancing Research Networking Systems.

    PubMed

    Schleyer, Titus; Butler, Brian S; Song, Mei; Spallek, Heiko

    2012-03-01

    Science in general, and biomedical research in particular, is becoming more collaborative. As a result, collaboration with the right individuals, teams, and institutions is increasingly crucial for scientific progress. We propose Research Networking Systems (RNS) as a new type of system designed to help scientists identify and choose collaborators, and suggest a corresponding research agenda. The research agenda covers four areas: foundations, presentation, architecture, and evaluation. Foundations includes project-, institution- and discipline-specific motivational factors; the role of social networks; and impression formation based on information beyond expertise and interests. Presentation addresses representing expertise in a comprehensive and up-to-date manner; the role of controlled vocabularies and folksonomies; the tension between seekers' need for comprehensive information and potential collaborators' desire to control how they are seen by others; and the need to support serendipitous discovery of collaborative opportunities. Architecture considers aggregation and synthesis of information from multiple sources, social system interoperability, and integration with the user's primary work context. Lastly, evaluation focuses on assessment of collaboration decisions, measurement of user-specific costs and benefits, and how the large-scale impact of RNS could be evaluated with longitudinal and naturalistic methods. We hope that this article stimulates the human-computer interaction, computer-supported cooperative work, and related communities to pursue a broad and comprehensive agenda for developing research networking systems.

  18. Conceptualizing and Advancing Research Networking Systems

    PubMed Central

    SCHLEYER, TITUS; BUTLER, BRIAN S.; SONG, MEI; SPALLEK, HEIKO

    2013-01-01

    Science in general, and biomedical research in particular, is becoming more collaborative. As a result, collaboration with the right individuals, teams, and institutions is increasingly crucial for scientific progress. We propose Research Networking Systems (RNS) as a new type of system designed to help scientists identify and choose collaborators, and suggest a corresponding research agenda. The research agenda covers four areas: foundations, presentation, architecture, and evaluation. Foundations includes project-, institution- and discipline-specific motivational factors; the role of social networks; and impression formation based on information beyond expertise and interests. Presentation addresses representing expertise in a comprehensive and up-to-date manner; the role of controlled vocabularies and folksonomies; the tension between seekers’ need for comprehensive information and potential collaborators’ desire to control how they are seen by others; and the need to support serendipitous discovery of collaborative opportunities. Architecture considers aggregation and synthesis of information from multiple sources, social system interoperability, and integration with the user’s primary work context. Lastly, evaluation focuses on assessment of collaboration decisions, measurement of user-specific costs and benefits, and how the large-scale impact of RNS could be evaluated with longitudinal and naturalistic methods. We hope that this article stimulates the human-computer interaction, computer-supported cooperative work, and related communities to pursue a broad and comprehensive agenda for developing research networking systems. PMID:24376309

  19. Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

    PubMed Central

    Tzvetkov, Mladen V.

    2008-01-01

    Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance. PMID:18224312

  20. National Research Networks Facilitate Mutually Beneficial Research at ARS Locations

    NASA Astrophysics Data System (ADS)

    Seyfried, M. S.; Holbrook, W. S.; Fellows, A.; Kormos, P.; Lohse, K. A.; Marks, D. G.; Flerchinger, G. N.

    2015-12-01

    A major benefit of participation in research networks such as the Long Term Agroecosystem Research (LTAR) network is that multidisciplinary research on a broad range of topics is facilitated. The interaction between the Agricultural Research Service long-term experimental watersheds and LTAR exemplifies this. At the Reynolds Creek Experimental Watershed (RCEW), this is further enhanced by participation in the Critical Zone Observatory (CZO) network. The RCEW has a long history (55 years) of experimentation, modeling and monitoring emphasizing hydrologic processes, which are inevitably related to biogeochemical processes, but rarely linked directly in RCEW research. New research with the Reynolds Creek CZO (RC CZO) emphasizes biogeochemistry. The background research and infrastructure at the RCEW provides an ideal platform for that research. At the same time, RC CZO products are enabling ARS to extend its research activities. We highlight three examples: (i) forcing data sets used to facilitate physical modeling of hydrologic and biogeochemical processes, (ii) linkage of hydrology and geophyscis to extend our understanding of subsurface processes, and (iii) climate/elevation linkages to ecosystem productivity, which are closely related in water limited environments such as the RCEW. The addition of the RCEW to the LTAR is further extended ARS capabilities. For example, the RCEW is now monitoring net carbon balance and productivity at sites along an elevation/climatic gradient. The addition of LTAR research enhances that work by extending the climate gradient and introducing management and land surface change effects. We anticipate that these interactions will grow and that cross-site experiments will be initiated as the results begin to accumulate.

  1. Pharmacogenetics: a reality or misplaced optimism?

    PubMed

    Mutsatsa, S; Currid, T J

    2013-04-01

    The paper aims to review current evidence that supports the application of genetic information in the management and use of psychotropic medication. Although the importance of an individual's genetic makeup in the metabolism of drugs has been known for at least 50 years, it is only recently that such information is finding clinical application. A literature review of recent studies suggest that there are clear variations in the way people respond to psychotropic medication. These variations can be seen across racial and ethnic lines, and are genetically determined. The hope is that, in future we will be able to use genetic information to predict which patient will benefit from which drug and at what dose. In other fields of health care such as anticoagulant therapy, the application of pharmacogenetics is now established in routine clinical care. Several psychiatric pharmacogenetic tests are currently available, including tests for the determination of metabolic status, risk of agranulocytosis and metabolic syndrome, and selection of beneficial medications. Since nurses are the centrepiece of mental health care, these advances are likely to alter significantly future mental health nurse education and practice.

  2. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine

    PubMed Central

    Ortega, Victor E; Meyers, Deborah A; Bleecker, Eugene R

    2015-01-01

    Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events. PMID:25691813

  3. Clinical Implementation of Germline Cancer Pharmacogenetic Variants during the Next-Generation Sequencing Era

    PubMed Central

    Gillis, Nancy K.; Patel, Jai N.; Innocenti, Federico

    2014-01-01

    Over 100 FDA-approved medications include pharmacogenetic biomarkers in the drug label, many with cancer indications referencing germline DNA variations. With the advent of next-generation sequencing (NGS) and its rapidly increasing uptake into cancer research and clinical practice, an enormous amount of data to inform documented gene-drug associations will be collected, which must be exploited to optimize patient benefit. This state-of-the-art article focuses on the implementation of germline cancer pharmacogenetics into clinical practice. Specifically, it discusses the importance of germline variation in cancer and the role of NGS in pharmacogenetic discovery and implementation. In the context of a scenario where massive NGS-based genetic information will be increasingly available to health stakeholders, this review explores the ongoing debate over the threshold of evidence necessary for implementation, provides an overview of recommendations in cancer by professional organizations and regulatory bodies, discusses limitations of current guidelines and strategies to improve third-party coverage. PMID:24136381

  4. Pharmacogenetics in psychiatry--a useful clinical tool or wishful thinking for the future?

    PubMed

    Kirchheiner, Julia; Seeringer, Angela; Viviani, Roberto

    2010-01-01

    More than fifty years of pharmacogenetic research have produced many examples of the impact of inherited variability in the response to psychotropic drugs. These successes, however, have as yet failed to translate into broadly applicable strategies for the improvement of individual drug treatment in psychiatry. One important argument against the widespread adoption of pharmacogenetics as a clinical tool is the lack of evidence showing its impact on medical decision making and on risk benefit ratio for the patients. The individual drug metabolizing capacity is assessed by genotyping drug metabolizing enzymes. The potential implications of information gained from genotyping are dose adjustments according to genotype. However, even when the consequences of genotype on pharmacokinetics are significant and well known, as in the case of many tricyclic antidepressants and several SSRIs, there is still considerable controversy on whether adjustment of dosage driven by genetic information may improve therapeutic efficacy, and/or adverse events is prevented, to an extent of any practical importance in clinical practice. Different types of pharmacogenetic studies may improve our understanding of the functional consequence of a genetic variant in the clinical setting. The use of intermediate phenotypes instead of broad outcome parameters such as drug response or remission might improve our knowledge on what exactly happens if an individual with a specific genotype takes a certain drug. Here, we review the potential impact of an integrated approach, including the assessment of intermediate phenotypes for the effect of genetic polymorphism, the monitoring of therapy progress, and response prediction in depression. PMID:20205659

  5. Pharmacogenetics and pharmacogenomics: recent developments, their clinical relevance and some ethical, social, and legal implications.

    PubMed

    Norbert, Paul W; Roses, Allen D

    2003-03-01

    In recent debates on novel procedures of molecular medicine pharmacogenomics is attracting more and more attention as a genotype-based approach for improving safety and efficacy of the use of therapeutic substances. Promoted by basic knowledge generated in the field of medical genomics, facilitated by novel technological tools for mapping genetic variation in individuals, and supported by results of initial clinical studies linking specific genotypes to metabolic characteristics of individuals important for assessing drug response, procedures of pharmacogenetics and pharmacogenomics now are starting to impact significantly on clinical research and development and medical practice. In this situation assessing the goals, risk, and benefits of pharmacogenetics and pharmacogenomics is essential for the medically successful, ethically justifiable, and socially acceptable implementation of genotype-based diagnosis and pharmacotherapy. We discuss the current state of the art in pharmacogenetics and pharmacogenomics and introduce a model for evidence based assessment of its goals, risk, and benefits. We differentiate here between pragmatic and normative issues in the development of pharmacogenomics in order to contrast prevailing, insufficiently interest-based modes of public technology assessment with the evidence-based mode that can be established as part of clinical study design. Finally, we provide a framework for the analysis of social accountability that can be used for technology development and technology assessment with regard to pharmacogenomics in particular and molecular medicine in general.

  6. Networking to Improve Nutrition Policy Research

    PubMed Central

    Blanck, Heidi M.; Cradock, Angie; Gortmaker, Steven

    2015-01-01

    Effective nutrition and obesity policies that improve the food environments in which Americans live, work, and play can have positive effects on the quality of human diets. The Centers for Disease Control and Prevention’s (CDC’s) Nutrition and Obesity Policy Research and Evaluation Network (NOPREN) conducts transdisciplinary practice-based policy research and evaluation to foster understanding of the effectiveness of nutrition policies. The articles in this special collection bring to light a set of policies that are being used across the United States. They add to the larger picture of policies that can work together over time to improve diet and health. PMID:26355829

  7. Networking to Improve Nutrition Policy Research.

    PubMed

    Kim, Sonia A; Blanck, Heidi M; Cradock, Angie; Gortmaker, Steven

    2015-09-10

    Effective nutrition and obesity policies that improve the food environments in which Americans live, work, and play can have positive effects on the quality of human diets. The Centers for Disease Control and Prevention's (CDC's) Nutrition and Obesity Policy Research and Evaluation Network (NOPREN) conducts transdisciplinary practice-based policy research and evaluation to foster understanding of the effectiveness of nutrition policies. The articles in this special collection bring to light a set of policies that are being used across the United States. They add to the larger picture of policies that can work together over time to improve diet and health.

  8. Delivering pharmacogenetic testing in a primary care setting

    PubMed Central

    Mills, Rachel; Voora, Deepak; Peyser, Bruce; Haga, Susanne B

    2013-01-01

    Pharmacogenetic testing refers to a type of genetic test to predict a patient’s likelihood to experience an adverse event or not respond to a given drug. Despite revision to several labels of commonly prescribed drugs regarding the impact of genetic variation, the use of this testing has been limited in many settings due to a number of factors. In the primary care setting, the limited office time as well as the limited knowledge and experience of primary care practitioners have likely attributed to the slow uptake of pharmacogenetic testing. This paper provides talking points for primary care physicians to discuss with patients when pharmacogenetic testing is warranted. As patients and physicians become more familiar and accepting of pharmacogenetic testing, it is anticipated that discussion time will be comparable to that of other clinical tests. PMID:24101877

  9. Reaching Out: IDRC-HDFS Research Network (India). Final Report.

    ERIC Educational Resources Information Center

    Saraswathi, T. S.; And Others

    This report documents the activities of the Research Network, a coordinated effort of the International Development Research Center (IDRC) and the Human Development and Family Studies (HDFS) Department of Baroda University (India) during the period January 1990 to June 1993. The Research Network aimed to establish a network of consultative…

  10. Warfarin pharmacogenetics: polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci in a genetically admixed Omani population.

    PubMed

    Pathare, Anil V; Al Zadjali, Shoaib; Misquith, Rhea; Alkindi, Salam S; Panjwani, Vinodh; Lapoumeroulie, Claudine; Pravin, Sahaya; Paldi, Andras; Krishnamoorthy, Rajagopal

    2012-02-01

    This is the first study to evaluate the spectrum and prevalence of dose-predictive genetic polymorphisms of the CYP2C9, CYP4F2 and VKORC1 loci together, in a geographically defined, ethnically admixed healthy adult Omani population sharing common lifestyle/environmental factors. Since the present-day Omani population is the result of an admixture of Caucasian, African and Asian ancestries, we compared the pharmacogenetic profile of these three loci in this population. Interestingly, the Omani pharmacogenetic profile, in terms of allele and genotype distribution, has values that are intermediate between Caucasians and African Americans, the African admixture further substantiated by the presence of the CYP2C9*8 allele. However, limitations and usefulness of such comparisons warrant caution, as the data from pharmacogenetic literature do not always represent bona fide population categories. Furthermore, definition of study population based on microgeographical scale would be more appropriate in pharmacogenetic research rather than the flawed racial, ethnic, or social categorizations since pharmacogenetic variation is clinal, and genetic influences will be further altered by lifestyle and environmental factors. PMID:22452429

  11. Research on 6R Military Logistics Network

    NASA Astrophysics Data System (ADS)

    Jie, Wan; Wen, Wang

    The building of military logistics network is an important issue for the construction of new forces. This paper has thrown out a concept model of 6R military logistics network model based on JIT. Then we conceive of axis spoke y logistics centers network, flexible 6R organizational network, lean 6R military information network based grid. And then the strategy and proposal for the construction of the three sub networks of 6Rmilitary logistics network are given.

  12. [Epilepsy pharmacogenetics : science or fiction?].

    PubMed

    Depondt, Chantal

    2013-02-01

    Pharmacogenetics (PGX) is the study of how genetic variants influence individual responses to drugs. Although numerous candidate gene studies in epilepsy PGX have been published, to date only two validated associations exist: the association of the *2 and *3 alleles of CYP2C9 with phenytoin metabolism and the association of HLA-B*1502 with serious hypersensitivity reactions to carbamazepine. The advent of novel technologies such as genomewide association studies and next generation sequencing will likely lead to the identification of additional genetic biomarkers. The potential benefits of epilepsy PGX are multiple: epilepsy treatment in individual patients would become more rationalized, clinical trials could be stratified according to patients' genetic profiles and novel therapeutic pathways may be uncovered. Ultimately, it is hoped that PGX will improve the quality of life for people suffering from epilepsy worldwide.

  13. Pharmacogenetic considerations in the treatment of gout.

    PubMed

    Roberts, Rebecca L; Stamp, Lisa K

    2015-01-01

    Gout is one of the most common forms of arthritis and the prevalence is increasing. Management comprises rapid and effective control of the inflammation in acute gout and sustained urate lowering in the long term. Improving the outcomes for cheaper old drugs and for the increasing number of new, more expensive agents is an important clinical goal. The role of pharmacogenetics in predicting response and adverse events to gout therapies is of considerable interest. Currently, prospective screening is employed to detect HLA-B*5801 carriage and glucose-6-phosphate dehydrogenase deficiency, to minimize occurrence of allopurinol hypersensitivity and pegloticase-related hemolytic anemia. In the future it is likely that other genetic markers of drug response will make the transition to clinical practice to further improve the efficacy and safety of gout therapies. In this review, we will examine the potential clinical relevance of specific genetic variants in the management of gout.

  14. Pharmacogenetics of treatment response in psoriatic arthritis.

    PubMed

    Jani, Meghna; Barton, Anne; Ho, Pauline

    2015-07-01

    TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice. In this review, we discuss the advances made in pharmacogenetics of treatment response in psoriatic arthritis to date, with focus on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline emerging methodologies to obtain data that will help inform a future precision medicine approach in this condition.

  15. A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy

    PubMed Central

    Bosch, Luis Ángel Bermúdez

    2014-01-01

    Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. PMID:25285240

  16. Pharmacogenetics of healthy volunteers in Puerto Rico.

    PubMed

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L; Duconge, Jorge

    2015-12-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  17. Pharmacogenetics of tacrolimus: ready for clinical translation?

    PubMed Central

    Coto, Eliecer; Tavira, Beatriz; Suárez-Álvarez, Beatriz; López-Larrea, Carlos; Díaz-Corte, Carmen; Ortega, Francisco; Álvarez, Victoria

    2011-01-01

    Tacrolimus (Tac) exhibits an interindividual pharmacokinetic variability that affects the dose required to reach the target concentration in blood. Tac is metabolized by two enzymes of the cytochrome P450 family, CYP3A5 and CYP3A4. The effect of the CYP3A5 genotype on Tac bioavailability has been demonstrated, and the main determinant of this pharmacogenetic effect is a single-nucleotide polymorphism (SNP) in intron 3 of CYP3A5 (6986 A>G; SNP rs776746; also known as CYP3A5*3). The mean dose-adjusted blood Tac concentration was significantly higher among CYP3A5*3 homozygotes than that of carriers of the wild-type allele (CYP3A5*1). In a recent prospective study, a group of kidney transplant patients received a Tac dose either according to the CYP3A5 genotype (the adapted group) or according to the standard regimen (the control group). All patients received induction therapy with mycophenolate mofetil, corticosteroids, and either basiliximab or intravenous anti-thymocyte globulin. Patients in the adapted-dose group required 3–8 days (median 6 days) to reach the target range compared with 3–25 days (median 7 days) in the control group (P=0.001). The total number of dose modifications was also lower in the adapted-dose group. This study also suggested that the CYP3A5 genotype might contribute minimally to the reduction of early acute rejection. However, additional studies are necessary to determine whether the pharmacogenetic approach could help reduce the necessity for induction therapy and co-immunosuppressors. PMID:25028625

  18. Pharmacogenetics of healthy volunteers in Puerto Rico.

    PubMed

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L; Duconge, Jorge

    2015-12-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island.

  19. Pharmacogenetics of healthy volunteers in Puerto Rico

    PubMed Central

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y.; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L.; Duconge, Jorge

    2016-01-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer’s disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  20. Medical research networks--an international comparison.

    PubMed

    Rienhoff, Otto

    2003-01-01

    Medical research networks (MRN) are described as a new approach in fostering science for health. It is described that this approach can be found in several countries and global business companies. MRNs try to maximise use of information technology (IT) for speeding up the long research and transfer process from basic science to patient care. Despite the fact that several countries have funding schemes for this approach, nomenclatures and frameworks vary due to different national conditions. Nevertheless there is a general expectation that MRNs are necessary. However, there long-term impact and efficiency has still to be evaluated. The results of this report are based on a benchmarking study currently underway in Germany. PMID:15061539

  1. Action research in developing knowledge networks.

    PubMed

    Seeley, Helen; Urquhart, Christine

    2008-12-01

    This paper describes the experiences of the Eastern Head Injury Study in creating a strategic regional head injury service framework using a collaborative action research methodology. The types of data, information and knowledge required to develop and support such a framework for both development and successful implementation are identified. This includes the identification of existing knowledge/information systems, the variability and gaps in these, and how the systems fit together, using a number of evidence-gathering and knowledge-sharing methods. The discussion debates the value of the action research approach and what principles are necessary in developing and maintaining knowledge networks. The project demonstrates that an understanding of the social learning cycle can help in understanding how the pieces fit together, and how the information systems need to be in place to provide the information (or data or knowledge) in the appropriate format to make the learning possible.

  2. Privacy Issues of a National Research and Education Network.

    ERIC Educational Resources Information Center

    Katz, James E.; Graveman, Richard F.

    1991-01-01

    Discussion of the right to privacy of communications focuses on privacy expectations within a National Research and Education Network (NREN). Highlights include privacy needs in scientific and education communications; academic and research networks; network security and privacy concerns; protection strategies; and consequences of privacy…

  3. Induction into Educational Research Networks: The Striated and the Smooth

    ERIC Educational Resources Information Center

    Hodgson, Naomi; Standish, Paul

    2006-01-01

    Educational research as an academic field can be understood as a network or group of networks and, therefore, to consist of interconnected nodes that structure the way the field operates and understands its purpose. This paper deals with the nature of the induction of postgraduate students into the network of educational research that takes place…

  4. Connecting the Dots: Understanding the Flow of Research Knowledge within a Research Brokering Network

    ERIC Educational Resources Information Center

    Rodway, Joelle

    2015-01-01

    Networks are frequently cited as an important knowledge mobilization strategy; however, there is little empirical research that considers how they connect research and practice. Taking a social network perspective, I explore how central office personnel find, understand and share research knowledge within a research brokering network. This mixed…

  5. Modern International Research Groups: Networks and Infrastructure

    NASA Astrophysics Data System (ADS)

    Katehi, Linda

    2009-05-01

    In a globalized economy, education and research are becoming increasing international in content and context. Academic and research institutions worldwide try to internationalize their programs by setting formal or informal collaborations. An education that is enhanced by international experiences leads to mobility of the science and technology workforce. Existing academic cultures and research structures are at odds with efforts to internationalize education. For the past 20-30 years, the US has recognized the need to improve the abroad experience of our scientists and technologists: however progress has been slow. Despite a number of both federally and privately supported programs, efforts to scale up the numbers of participants have not been satisfactory. The exchange is imbalanced as more foreign scientists and researchers move to the US than the other way around. There are a number of issues that contribute to this imbalance but we could consider the US academic career system, as defined by its policies and practices, as a barrier to internationalizing the early career faculty experience. Strict curricula, pre-tenure policies and financial commitments discourage students, post doctoral fellows and pre-tenure faculty from taking international leaves to participate in research abroad experiences. Specifically, achieving an international experience requires funding that is not provided by the universities. Furthermore, intellectual property requirements and constraints in pre-tenure probationary periods may discourage students and faculty from collaborations with peers across the Atlantic or Pacific or across the American continent. Environments that support early career networking are not available. This presentation will discuss the increasing need for international collaborations and will explore the need for additional programs, more integration, better conditions and improved infrastructures that can encourage and support mobility of scientists. In addition

  6. The APA and the rise of pediatric generalist network research.

    PubMed

    Wasserman, Richard; Serwint, Janet R; Kuppermann, Nathan; Srivastava, Rajendu; Dreyer, Benard

    2011-01-01

    The Academic Pediatric Association (APA, formerly the Ambulatory Pediatric Association) first encouraged multi-institutional collaborative research among its members over 30 years ago. Individual APA members subsequently went on to figure prominently in establishing formal research networks. These enduring collaborations have been established to conduct investigations in a variety of generalist contexts. At present, 4 generalist networks--Pediatric Research in Office Settings (PROS), the Pediatric Emergency Care Applied Research Network (PECARN), the COntinuity Research NETwork (CORNET), and Pediatric Research in Inpatient Settings (PRIS)--have a track record of extensive achievement in generating new knowledge aimed at improving the health and health care of children. This review details the history, accomplishments, and future directions of these networks and summarizes the common themes, strengths, challenges, and opportunities inherent in pediatric generalist network research.

  7. Action Research Networks: Role and Purpose in the Evaluation of Research Outcomes and Impacts

    ERIC Educational Resources Information Center

    Zornes, Deborah; Ferkins, Lesley; Piggot-Irvine, Eileen

    2016-01-01

    The focus of this paper is to share thinking about networks in action research (AR) and to consider their role, purpose, and how networks' outcomes and impacts might be evaluated. Networks are often a by-product of AR projects, yet research focused on the network itself as part of a project is rare. The paper is one of several associated with the…

  8. Pharmacogenetics and pharmacogenomics as tools in cancer therapy.

    PubMed

    Rodríguez-Vicente, Ana E; Lumbreras, Eva; Hernández, Jesus M; Martín, Miguel; Calles, Antonio; Otín, Carlos López; Algarra, Salvador Martín; Páez, David; Taron, Miquel

    2016-03-01

    Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments. Specifically, we present recent progress in breast cancer molecular classifiers, cell-free circulating DNA as a prognostic and predictive biomarker in cancer, patient-derived tumor xenograft models, chronic lymphocytic leukemia genomic landscape, and current pharmacogenetic advances in colorectal cancer. This review is based on the lectures presented by the speakers of the symposium "Pharmacogenetics and Pharmacogenomics as Tools in Cancer Therapy" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF), held in Madrid (Spain) on April 21, 2015.

  9. Molecular actions and clinical pharmacogenetics of lithium therapy

    PubMed Central

    Can, Adem; Schulze, Thomas G.; Gould, Todd D.

    2014-01-01

    Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future. PMID:24534415

  10. Molecular actions and clinical pharmacogenetics of lithium therapy.

    PubMed

    Can, Adem; Schulze, Thomas G; Gould, Todd D

    2014-08-01

    Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium's therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

  11. Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management.

    PubMed

    Ortega, V E

    2014-07-01

    Beta2 (β2) adrenergic receptor agonists (beta agonists) are a commonly prescribed treatment for asthma despite the small increase in risk for life-threatening adverse responses associated with long-acting beta agonist (LABA). The concern for life-threatening adverse effects associated with LABA and the inter-individual variability of therapeutic responsiveness to LABA-containing combination therapies provide the rationale for pharmacogenetic studies of beta agonists. These studies primarily evaluated genes within the β2-adrenergic receptor and related pathways; however, recent genome-wide studies have identified novel loci for beta agonist response. Recent studies have identified a role for rare genetic variants in determining beta agonist response and, potentially, the risk for rare, adverse responses to LABA. Before genomics research can be applied to the development of genetic profiles for personalized medicine, it will be necessary to continue adapting to the analysis of an increasing volume of genetic data in larger cohorts with a combination of analytical methods and in vitro studies.

  12. Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia: Pharmacogenetics of Statins.

    PubMed

    Ruaño, Gualberto; Seip, Richard; Windemuth, Andreas; Wu, Alan H B; Thompson, Paul D

    2016-09-01

    Statin responsiveness is an area of great research interest given the success of the drug class in the treatment of hypercholesterolemia and in primary and secondary prevention of cardiovascular disease. Interrogation of the patient's genome for gene variants will eventually guide anti-hyperlipidemic intervention. In this review, we discuss methodological approaches to discover genetic markers predictive of class-wide and drug-specific statin efficacy and safety. Notable pharmacogenetic findings are summarized from hypothesis-free genome wide and hypothesis-led candidate gene association studies. Physiogenomic models and clinical decision support systems will be required for DNA-guided statin therapy to reach practical use in medicine. PMID:27514463

  13. Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia: Pharmacogenetics of Statins.

    PubMed

    Ruaño, Gualberto; Seip, Richard; Windemuth, Andreas; Wu, Alan H B; Thompson, Paul D

    2016-09-01

    Statin responsiveness is an area of great research interest given the success of the drug class in the treatment of hypercholesterolemia and in primary and secondary prevention of cardiovascular disease. Interrogation of the patient's genome for gene variants will eventually guide anti-hyperlipidemic intervention. In this review, we discuss methodological approaches to discover genetic markers predictive of class-wide and drug-specific statin efficacy and safety. Notable pharmacogenetic findings are summarized from hypothesis-free genome wide and hypothesis-led candidate gene association studies. Physiogenomic models and clinical decision support systems will be required for DNA-guided statin therapy to reach practical use in medicine.

  14. Recent research in network problems with applications

    NASA Technical Reports Server (NTRS)

    Thompson, G. L.

    1980-01-01

    The capabilities of network codes and their extensions are surveyed in regard to specially structured integer programming problems which are solved by using the solutions of a series of ordinary network problems.

  15. [Pharmacogenetics and prediction of side effects of drugs].

    PubMed

    Harrak, Mohammed; Khabbal, Youssef; Amarti, Afaf; El Hassouni, Mohammed; Ouldim, Karim

    2014-01-01

    Drug response is often variable from one individual to another, which sometimes makes them difficult to use when the therapeutic range is narrow. This interindividual variability in response can be explained in part by genetic factors affecting the metabolism, transport and the mechanism of action of drugs. Pharmacogenetics studies the genetic mechanisms involved in the response to drugs in order to optimize drug therapy, both in terms of efficacy and job security. This article summarizes the most known present clinical applications that illustrate the benefit of pharmacogenetic tests available to the clinician and are feasible for routine therapeutic management of patients (prediction of efficacy and toxicity of drugs), but also to demonstrate the benefit of pharmacogenetic tests in terms of health economics (reducing the incidence of hospitalizations for adverse drug events).

  16. Pharmacogenetics of antipsychotic-induced side effects

    PubMed Central

    Lencz, Todd; Malhotra, Anil K.

    2009-01-01

    Currently available antipsychotic drugs (APDs) carry significant, though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardr inesia (TD) and for an effect of variation at the receptor gene (HTR2C) for liability to APD-inducec gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are revieved in this article. PMID:20135898

  17. Pharmacogenetics of SSRIs and Sexual Dysfunction

    PubMed Central

    Osis, Liana; Bishop, Jeffrey R.

    2010-01-01

    Sexual dysfunction (SD) is a common and disconcerting side effect of selective serotonin reuptake inhibitors (SSRIs) that often influences a patient’s desire to continue long-term antidepressant treatment. Studies specifically assessing changes in sexual well-being over time illustrate that the incidence of sexual side effects from SSRIs ranges from 20% to 70%, depending on the characteristics of the study sample assessed. Developing strategies to predict who may be at the highest risk for adverse changes in their sexual well-being is an important step in improving the quality of life and treatment of patients who require antidepressant therapy. Pharmacogenetic studies of SSRI-associated SD have identified associations between serotonin and glutamate system genes with aspects of SD. The results of studies investigating genetic variations in drug metabolism enzymes and their relationships to antidepressant-associated adverse effects have been mixed. Continued efforts to characterize the relationships between genetic markers and antidepressant outcomes, and to translate this knowledge to patient care, have the potential to significantly improve the empiric selection of antidepressant agents and to minimize the risk for intolerable side effects.

  18. Pharmacogenetics of second-generation antipsychotics.

    PubMed

    Brennan, Mark D

    2014-04-01

    This review considers pharmacogenetics of the so called 'second-generation' antipsychotics. Findings for polymorphisms replicating in more than one study are emphasized and compared and contrasted with larger-scale candidate gene studies and genome-wide association study analyses. Variants in three types of genes are discussed: pharmacokinetic genes associated with drug metabolism and disposition, pharmacodynamic genes encoding drug targets, and pharmacotypic genes impacting disease presentation and subtype. Among pharmacokinetic markers, CYP2D6 metabolizer phenotype has clear clinical significance, as it impacts dosing considerations for aripiprazole, iloperidone and risperidone, and variants of the ABCB1 gene hold promise as biomarkers for dosing for olanzapine and clozapine. Among pharmacodynamic variants, the TaqIA1 allele of the DRD2 gene, the DRD3 (Ser9Gly) polymorphism, and the HTR2C -759C/T polymorphism have emerged as potential biomarkers for response and/or side effects. However, large-scale candidate gene studies and genome-wide association studies indicate that pharmacotypic genes may ultimately prove to be the richest source of biomarkers for response and side effect profiles for second-generation antipsychotics.

  19. Pharmacogenetics of drug response in Parkinson's disease.

    PubMed

    Džoljić, Eleonora; Novaković, Ivana; Krajinovic, Maja; Grbatinić, Ivan; Kostić, Vladimir

    2015-01-01

    Parkinson's disease (PD) is a debilitating, demoralizing and financially devastating condition affecting 1% of population at the age of 60 years. Thus, very important issue to address is individual therapy optimization. Recent results have shown evidence that variable efficacy of treatment and risk of motor and mental complications could have genetic origin. Significant roles in that process play (pharmaco)genomic/genetic studies of PD. Variability in genes coding for drug-metabolizing enzymes, drug receptors and proteins involved in drug pathway signaling is an important factor determining inter-individual variability in drug responses. Interpersonal differences in drug responses are clearly documented although individualized treatment of PD is not widely known. Treatment with antiparkinsonian drugs is associated with the development of complications, such as L-DOPA-induced dyskinesia (LID), hallucinations and excessive daytime sleepiness. Carriers of specific genetic polymorphisms are particularly susceptible to development of some of these drug adverse effects. Pharmacogenomics aims to understand the relationship between genetic factors and inter-individual variations in drug responses, and to translate this information in therapy tailored to individual patient genetics. Relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. Thus, many genetic variations and polymorphisms in myriad of different proteins can influence individual response to anti-PD drugs.

  20. Pharmacogenetic analysis of clinically relevant genetic polymorphisms.

    PubMed

    McLeod, Howard L

    2005-11-15

    The ascertainment of the human genome sequence has generated great enthusiasm for the use of gene-based approaches to improve virtually all aspects of medical care. Particular interest has focused on the field of pharmacogenetics--for example, the use of an individual's genetic profile to optimize drug prescription. This approach takes advantage of the presence of single-nucleotide polymorphisms (SNPs) or other genetic variants in every gene in the human genome. There are currently > 9 million SNPs in the human SNP database dbSNP, with an estimated 11 million variants ultimately to be found in the human population. To date, the preponderance of interest in this field has centered on the potential of applying this approach to subacute or chronic illnesses, such as cancer, cardiovascular disease, human immunodeficiency virus infection, or rheumatologic disorders. In contrast, little attention has been devoted to the potential utility of implementing the pharmacogenomic methodology for guiding drug selection for acutely ill patients in the critical care environment. Although such an approach has theoretical appeal as a means of enhancing quality and improving outcomes in this setting, several obstacles currently exist and slow the progress toward clinical application. PMID:16237646

  1. Enabling collaborative research using the Biomedical Informatics Research Network (BIRN)

    PubMed Central

    Ambite, Jose Luis; Ames, Joseph; Ananthakrishnan, Rachana; Burns, Gully; Chervenak, Ann L; Foster, Ian; Liming, Lee; Keator, David; Macciardi, Fabio; Madduri, Ravi; Navarro, John-Paul; Potkin, Steven; Rosen, Bruce; Ruffins, Seth; Schuler, Robert; Turner, Jessica A; Toga, Arthur; Williams, Christina; Kesselman, Carl

    2011-01-01

    Objective As biomedical technology becomes increasingly sophisticated, researchers can probe ever more subtle effects with the added requirement that the investigation of small effects often requires the acquisition of large amounts of data. In biomedicine, these data are often acquired at, and later shared between, multiple sites. There are both technological and sociological hurdles to be overcome for data to be passed between researchers and later made accessible to the larger scientific community. The goal of the Biomedical Informatics Research Network (BIRN) is to address the challenges inherent in biomedical data sharing. Materials and methods BIRN tools are grouped into ‘capabilities’ and are available in the areas of data management, data security, information integration, and knowledge engineering. BIRN has a user-driven focus and employs a layered architectural approach that promotes reuse of infrastructure. BIRN tools are designed to be modular and therefore can work with pre-existing tools. BIRN users can choose the capabilities most useful for their application, while not having to ensure that their project conforms to a monolithic architecture. Results BIRN has implemented a new software-based data-sharing infrastructure that has been put to use in many different domains within biomedicine. BIRN is actively involved in outreach to the broader biomedical community to form working partnerships. Conclusion BIRN's mission is to provide capabilities and services related to data sharing to the biomedical research community. It does this by forming partnerships and solving specific, user-driven problems whose solutions are then available for use by other groups. PMID:21515543

  2. Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies

    PubMed Central

    Daily, Elizabeth B; Aquilante, Christina L

    2009-01-01

    Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8 polymorphisms on substrate disposition in humans has been investigated in a number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical data suggest that the CYP2C8*3 allele is associated with increased metabolism of the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3 allele on the disposition of NSAIDs are conflicting and no definitive conclusions can be made at this time. The purpose of this review is to highlight these clinical studies that have investigated the association between CYP2C8 polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research. PMID:19761371

  3. EARLINET: potential operationality of a research network

    NASA Astrophysics Data System (ADS)

    Sicard, M.; D'Amico, G.; Comerón, A.; Mona, L.; Alados-Arboledas, L.; Amodeo, A.; Baars, H.; Baldasano, J. M.; Belegante, L.; Binietoglou, I.; Bravo-Aranda, J. A.; Fernández, A. J.; Fréville, P.; García-Vizcaíno, D.; Giunta, A.; Granados-Muñoz, M. J.; Guerrero-Rascado, J. L.; Hadjimitsis, D.; Haefele, A.; Hervo, M.; Iarlori, M.; Kokkalis, P.; Lange, D.; Mamouri, R. E.; Mattis, I.; Molero, F.; Montoux, N.; Muñoz, A.; Muñoz Porcar, C.; Navas-Guzmán, F.; Nicolae, D.; Nisantzi, A.; Papagiannopoulos, N.; Papayannis, A.; Pereira, S.; Preißler, J.; Pujadas, M.; Rizi, V.; Rocadenbosch, F.; Sellegri, K.; Simeonov, V.; Tsaknakis, G.; Wagner, F.; Pappalardo, G.

    2015-11-01

    In the framework of ACTRIS (Aerosols, Clouds, and Trace Gases Research Infrastructure Network) summer 2012 measurement campaign (8 June-17 July 2012), EARLINET organized and performed a controlled exercise of feasibility to demonstrate its potential to perform operational, coordinated measurements and deliver products in near-real time. Eleven lidar stations participated in the exercise which started on 9 July 2012 at 06:00 UT and ended 72 h later on 12 July at 06:00 UT. For the first time, the single calculus chain (SCC) - the common calculus chain developed within EARLINET for the automatic evaluation of lidar data from raw signals up to the final products - was used. All stations sent in real-time measurements of a 1 h duration to the SCC server in a predefined netcdf file format. The pre-processing of the data was performed in real time by the SCC, while the optical processing was performed in near-real time after the exercise ended. 98 and 79 % of the files sent to SCC were successfully pre-processed and processed, respectively. Those percentages are quite large taking into account that no cloud screening was performed on the lidar data. The paper draws present and future SCC users' attention to the most critical parameters of the SCC product configuration and their possible optimal value but also to the limitations inherent to the raw data. The continuous use of SCC direct and derived products in heterogeneous conditions is used to demonstrate two potential applications of EARLINET infrastructure: the monitoring of a Saharan dust intrusion event and the evaluation of two dust transport models. The efforts made to define the measurements protocol and to configure properly the SCC pave the way for applying this protocol for specific applications such as the monitoring of special events, atmospheric modeling, climate research and calibration/validation activities of spaceborne observations.

  4. The Security Research of Digital Library Network

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Song, Ding-Li; Yan, Shu

    Digital library is a self-development needs for the modern library to meet the development requirements of the times, changing the way services and so on. digital library from the hardware, technology, management and other aspects to objective analysis of the factors of threats to digital library network security. We should face up the problems of digital library network security: digital library network hardware are "not hard", the technology of digital library is relatively lag, digital library management system is imperfect and other problems; the government should take active measures to ensure that the library funding, to enhance the level of network hardware, to upgrade LAN and prevention technology, to improve network control technology, network monitoring technology; to strengthen safety management concepts, to prefect the safety management system; and to improve the level of security management modernization for digital library.

  5. Social network analysis of interdisciplinarity in obesity research.

    PubMed

    Bales, Michael; Johnson, Stephen B; Weng, Chunhua

    2008-11-06

    Transdisciplinary research accelerates scientific progress. Despite the value of social network analysis to characterize interdepartmental collaboration, institutions have been slow to adopt the approach. We use the approach to characterize collaboration among obesity researchers at our institution, identifying cores of researchers engaged in frequent collaborations. Providing an objective view of research across an institution, social network analysis is a baseline for efforts to facilitate transdisciplinary collaboration.

  6. South African Human Sciences Research Networking Directory. First Edition.

    ERIC Educational Resources Information Center

    van der Berg, Henda, Ed.; Maree-Snijders, Asa, Ed.; Prinsloo, Roelf, Ed.

    This networking directory is a comprehensive reference source of names, locations, and fields of interest of South African human sciences researchers. The guide is intended to promote research cooperation, facilitate networking, and organize conferences. The directory is intended for use at both the international level and the local level. The…

  7. How Might Better Network Theories Support School Leadership Research?

    ERIC Educational Resources Information Center

    Hadfield, Mark; Jopling, Michael

    2012-01-01

    This article explores how recent research in education has applied different aspects of "network" theory to the study of school leadership. Constructs from different network theories are often used because of their perceived potential to clarify two perennial issues in leadership research. The first is the relative importance of formal and…

  8. Pharmacogenetics of isoniazid-induced hepatotoxicity.

    PubMed

    Perwitasari, Dyah Aryani; Atthobari, Jarir; Wilffert, Bob

    2015-05-01

    Tuberculosis is still a major problem in some developed and developing countries. The poor compliance to the treatment of tuberculosis patients due to the adverse events was supposed to be an important factor contributing to the high prevalence. This review aims to clarify the role and the pharmacological mechanism of the genes involved in the isoniazid-induced hepatotoxicity. We selected English articles of studies in human from PubMed up to May 2014 with the keywords pharmacogenetic, isoniazid and hepatotoxicity, N-acetyl transferase 2 (NAT2), CYP2E1 and glutathione S transferase (GST). Polymorphisms of NAT2, CYP2E1 and GST1 could increase patients' susceptibility to isoniazid-induced hepatotoxicity. The rapid acetylators of NAT2 and rapid metabolizers of CYP2E1 showed increased concentrations of hepatotoxic metabolites. However, the rapid metabolizers of GST1 could decrease the concentration of hepatotoxic metabolites. Some studies of human leukocyte antigen (HLA), Uridine 5'-dipphospho (UDP) glucuronosyltransferase (UGT), nitric oxide synthase (NOS), Broad complex, Tramtrack, Bric-a-brac (BTB) and cap'n'collar type of basic region leucine zipper factor family (CNC) homolog (BACH) and Maf basic leucine zipper protein (MAFK) polymorphisms showed their roles in isoniazid-induced hepatotoxicity by modifying the expression of antioxidant enzymes. A better insight into the role of polymorphisms of HLA, UGT, NOS, BACH and MAFK in addition to NAT2, CYP2E1 and GST1 in the hepatotoxicity of isoniazid may support physicians in monitoring patients hepatotoxicity symptoms and laboratory data and optimizing pharmacotherapy. Future studies about the role of such polymorphisms in different ethnicities are suggested. PMID:26095714

  9. Pharmacogenetics of the antiplatelet effect of aspirin.

    PubMed

    Würtz, Morten; Kristensen, Steen Dalby; Hvas, Anne-Mette; Grove, Erik Lerkevang

    2012-01-01

    The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical, pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ibα), cyclooxygenases (1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2 receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa has been associated with a reduced antiplatelet effect of aspirin. The additive value of an individual's genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations considered to influence the antiplatelet effect of aspirin.

  10. Cognitive radio wireless sensor networks: applications, challenges and research trends.

    PubMed

    Joshi, Gyanendra Prasad; Nam, Seung Yeob; Kim, Sung Won

    2013-08-22

    A cognitive radio wireless sensor network is one of the candidate areas where cognitive techniques can be used for opportunistic spectrum access. Research in this area is still in its infancy, but it is progressing rapidly. The aim of this study is to classify the existing literature of this fast emerging application area of cognitive radio wireless sensor networks, highlight the key research that has already been undertaken, and indicate open problems. This paper describes the advantages of cognitive radio wireless sensor networks, the difference between ad hoc cognitive radio networks, wireless sensor networks, and cognitive radio wireless sensor networks, potential application areas of cognitive radio wireless sensor networks, challenges and research trend in cognitive radio wireless sensor networks. The sensing schemes suited for cognitive radio wireless sensor networks scenarios are discussed with an emphasis on cooperation and spectrum access methods that ensure the availability of the required QoS. Finally, this paper lists several open research challenges aimed at drawing the attention of the readers toward the important issues that need to be addressed before the vision of completely autonomous cognitive radio wireless sensor networks can be realized.

  11. Cognitive Radio Wireless Sensor Networks: Applications, Challenges and Research Trends

    PubMed Central

    Joshi, Gyanendra Prasad; Nam, Seung Yeob; Kim, Sung Won

    2013-01-01

    A cognitive radio wireless sensor network is one of the candidate areas where cognitive techniques can be used for opportunistic spectrum access. Research in this area is still in its infancy, but it is progressing rapidly. The aim of this study is to classify the existing literature of this fast emerging application area of cognitive radio wireless sensor networks, highlight the key research that has already been undertaken, and indicate open problems. This paper describes the advantages of cognitive radio wireless sensor networks, the difference between ad hoc cognitive radio networks, wireless sensor networks, and cognitive radio wireless sensor networks, potential application areas of cognitive radio wireless sensor networks, challenges and research trend in cognitive radio wireless sensor networks. The sensing schemes suited for cognitive radio wireless sensor networks scenarios are discussed with an emphasis on cooperation and spectrum access methods that ensure the availability of the required QoS. Finally, this paper lists several open research challenges aimed at drawing the attention of the readers toward the important issues that need to be addressed before the vision of completely autonomous cognitive radio wireless sensor networks can be realized. PMID:23974152

  12. The Patient-Centered Outcomes Research Network: a national infrastructure for comparative effectiveness research.

    PubMed

    Califf, Robert M

    2014-01-01

    The current clinical research system does not produce high-quality evidence quickly enough to support health care decision making. The Patient-Centered Outcomes Research Network (PCORnet) embodies a novel strategy for creating a national "network of networks" that is capable of significantly accelerating evidence generation to support a learning health system.

  13. Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

    PubMed Central

    Duconge, Jorge; Cadilla, Carmen L.; Ruaño, Gualberto

    2015-01-01

    Although the Hispanic population is continuously growing in the United States, they are underrepresented in pharmacogenetic studies. This review addresses the need for compiling available pharmacogenetic data in US Hispanics, discussing the prevalence of clinically relevant polymorphisms in pharmacogenes encoding for drug-metabolizing enzymes. CYP3A5*3 (0.245–0.867) showed the largest frequency in a US Hispanic population. A higher prevalence of CYP2C9*3, CYP2C19*4, and UGT2B7 IVS1+985 A>Gwas observed in US Hispanic vs. non-Hispanic populations. We found interethnic and intraethnic variability in frequencies of genetic polymorphisms for metabolizing enzymes, which highlights the need to define the ancestries of participants in pharmacogenetic studies. New approaches should be integrated in experimental designs to gain knowledge about the clinical relevance of the unique combination of genetic variants occurring in this admixed population. Ethnic subgroups in the US Hispanic population may harbor variants that might be part of multiple causative loci or in linkage-disequilibrium with functional variants. Pharmacogenetic studies in Hispanics should not be limited to ascertain commonly studied polymorphisms that were originally identified in their parental populations. The success of the Personalized Medicine paradigm will depend on recognizing genetic diversity between and within US Hispanics and the uniqueness of their genetic backgrounds. PMID:25431893

  14. Pharmacogenetics of the Neurodevelopmental Impact of Anticancer Chemotherapy

    ERIC Educational Resources Information Center

    Robaey, Philippe; Krajinovic, Maja; Marcoux, Sophie; Moghrabi, Albert

    2008-01-01

    Pharmacogenetics holds the promise of minimizing adverse neurodevelopmental outcomes of cancer patients by identifying patients at risk, enabling the individualization of treatment and the planning of close follow-up and early remediation. This review focuses first on methotrexate, a drug often implicated in neurotoxicity, especially when used in…

  15. Challenges and pitfalls in the introduction of pharmacogenetics for cancer.

    PubMed

    Loh, Marie; Soong, Richie

    2011-08-01

    There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer and VKORC1 genotyping for warfarin dosing in thrombosis. Encouraging results from these studies suggest that genetic factors may indeed be important determinants of drug response and toxicity for at least some drugs. However, to apply pharmacogenetics appropriately, a thorough understanding of the scope and limitations of this field is required. The challenges include an appreciation of biological variability, logistical issues pertaining to the proper management of information, the need for robust methods and adequate sample quality with well-designed workflows. At the same time, the economics of pharmacogenetic testing from the perspective of clinicians, patients, governments, insurance companies and pharmaceutical companies will play an important role in determining its future use. Ethical considerations such as informed consent and patient privacy, as well as the role of regulatory bodies in addressing these issues, must be fully understood. Only once these issues are properly dealt with can the full benefits of pharmacogenetics begin to be realised.

  16. Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

    PubMed Central

    Provenzani, Alessio; Santeusanio, Andrew; Mathis, Erin; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Provenzani, Ambra; Polidori, Carlo; Vizzini, Giovanni; Polidori, Piera; D’Alessandro, Natale

    2013-01-01

    The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing. PMID:24409044

  17. US computer research networks: Domestic and international telecommunications capacity requirements

    NASA Technical Reports Server (NTRS)

    Kratochvil, D.; Sood, D.

    1990-01-01

    The future telecommunications capacity and connectivity requirements of the United States (US) research and development (R&D) community raise two concerns. First, would there be adequate privately-owned communications capacity to meet the ever-increasing requirements of the US R&D community for domestic and international connectivity? Second, is the method of piecemeal implementation of communications facilities by individual researchers cost effective when viewed from an integrated perspective? To address the capacity issue, Contel recently completed a study for NASA identifying the current domestic R&D telecommunications capacity and connectivity requirements, and projecting the same to the years 1991, 1996, 2000, and 2010. The work reported here extends the scope of an earlier study by factoring in the impact of international connectivity requirements on capacity and connectivity forecasts. Most researchers in foreign countries, as is the case with US researchers, rely on regional, national or continent-wide networks to collaborate with each other, and their US counterparts. The US researchers' international connectivity requirements, therefore, stem from the need to link the US domestic research networks to foreign research networks. The number of links and, more importantly, the speeds of links are invariably determined by the characteristics of the networks being linked. The major thrust of this study, therefore, was to identify and characterize the foreign research networks, to quantify the current status of their connectivity to the US networks, and to project growth in the connectivity requirements to years 1991, 1996, 2000, and 2010 so that a composite picture of the US research networks in the same years could be forecasted. The current (1990) US integrated research network, and its connectivity to foreign research networks is shown. As an example of projections, the same for the year 2010 is shown.

  18. The ETH Flux Research Network ("Swiss Fluxnet")

    NASA Astrophysics Data System (ADS)

    Eugster, W.; Zeeman, M. J.; Häsler, R.; Buchmann, N.

    2006-12-01

    Within CarboEurope more than 100 eddy covariance flux towers aim at providing spatially representative CO2 and energy fluxes from the major forest ecosystem types, grasslands, and croplands. Still, at the regional (10's of km) scale the spatial variation in topography and ecosystem types is not adequately represented in mountainous areas such as Switzerland. Therefore we have extended the cluster of three CarboEurope flux sites (Oensingen grassland; Oensingen cropland; Laegeren mixed forest) by additional sites that form an elevational transect from the low elevations of the Swiss Plateau (around 400 m a.s.l.) to the interior of the Central Alps (around 2000 m a.s.l.). As of 2006 there were the following sites operated by this research group: Elevation Ecosystem Location Since Type 2000 m Alpine pasture Crap Alv ETH 2005 seasonal 1640 m Subalpine coniferous forest Davos 1997 continuous 1000 m Montane Grassland Früebüel ETH 2006 continuous 0700 m Montane mixed forest Lägeren 2004 continuous 0400 m Lowland Grassland Chamau ETH 2006 continuous 0400 m Cropland Oensingen 2004 continuous In addition to the CarboEurope network design these sites attempt to cover all agriculturally important ecosystems in Switzerland, which are characterized by a seasonal three-stage management system where cattle are moved from their winter pastures in the lowlands to the montane meadows in spring, followed by the summer pastures above the treeline in the Alps. At the same time the two forest sites cover the two most important types with deciduous trees (beech, maple, ash) dominated mixed forest at lower elevations, and Norway spruce near the Alpine treeline. The long-term flux research to be carried out along this elevational transect will allow us to gain a better understanding of how elevation---and thus a very steep climate gradient over a relatively short horizontal distance---interrelate with land use and land management. This will greatly help to increase our ability to predict

  19. Direct PCR: a new pharmacogenetic approach for the inexpensive testing of HLA-B*57:01

    PubMed Central

    Cascella, R; Strafella, C; Ragazzo, M; Zampatti, S; Borgiani, P; Gambardella, S; Pirazzoli, A; Novelli, G; Giardina, E

    2015-01-01

    One of the most successful applications of pharmacogenetics research is the genetic screening for HLA-B*57:01, strongly associated with an increased risk to develop hypersensitivity reaction in HIV-positive patients following abacavir administration. Taking into consideration the limits of current genotyping methodologies, we have developed and validated (150 buccal swabs) an inexpensive pharmacogenetic approach for HLA-B*57:01 typing. In our assay DNA extraction and amplification are combined in one single step (direct PCR protocol), which is performed directly on the biological sample without the need of extraction and sequencing passages. The amplicons obtained by direct PCR can be easily separated on the agarose gel under ultraviolet. As per our results, the direct PCR represents a good alternative to the traditional methods of HLA-B*57:01 pharmacogenetic test, especially for those laboratories or countries where currently available approaches are often not available or not affordable. Furthermore it is an innovative approach, promoting a personalized, safer and cost-effective therapy. PMID:25201286

  20. Taking part in a pharmacogenetic clinical trial: assessment of trial participants understanding of information disclosed during the informed consent process

    PubMed Central

    2013-01-01

    Background This study is the first to examine the understandings that participants have of the consent process in a pharmacogenetic trial of anti-depressant medication. Methods This was a qualitative cross sectional study. There were 76 participants residing in London, Mannheim, Arhuus and Poznan. Results Only one quarter of participants (none in Poznan) could articulate the concept of pharmacogenetics. Heritability and testing medication were also given as the purpose of the trial. Most participants had not appreciated harms that could derive from the trial. Even when shown the consent sheet, participants were confused about DNA profiling. There was evidence that participants appreciated weekly contact with researchers. Most said they would participate in a trial again but would like choice over the intervention they were assigned to. Conclusion Participants in this study showed a poor level of informed consent. Although this is not the first time this argument has been made, it is in the case of a pharmacogenetic trial. Further work should investigate the associations between extraneous factors such as information and social support on beneficial or untoward outcomes of antidepressant treatment. PMID:24025622

  1. Research on scheme of applying ASON to current networks

    NASA Astrophysics Data System (ADS)

    Mao, Y. F.; Li, J. R.; Deng, L. J.

    2008-10-01

    Automatically Switched Optical Network (ASON) is currently a new and hot research subject in the world. It can provide high bandwidth, high assembly flexibility, high network security and reliability, but with a low management cost. It is presented to meet the requirements for high-throughput optical access with stringent Quality of Service (QoS). But as a brand new technology, ASON can not be supported by the traditional protocol software and network equipments. And the approach to build a new ASON network on the basis of completely abandoning the traditional optical network facilities is not desirable, because it costs too much and wastes a lot of network resources can also be used. So how to apply ASON to the current networks and realize the smooth transition between the existing network and ASON has been a serious problem to many network operators. In this research, the status in quo of ASON is introduced first and then the key problems should be considered when applying ASON to current networks are discussed. Based on this, the strategies should be complied with to overcome these key problems are listed. At last, the approach to apply ASON to the current optical networks is proposed and analyzed.

  2. Increasing Scalability of Researcher Network Extraction from the Web

    NASA Astrophysics Data System (ADS)

    Asada, Yohei; Matsuo, Yutaka; Ishizuka, Mitsuru

    Social networks, which describe relations among people or organizations as a network, have recently attracted attention. With the help of a social network, we can analyze the structure of a community and thereby promote efficient communications within it. We investigate the problem of extracting a network of researchers from the Web, to assist efficient cooperation among researchers. Our method uses a search engine to get the cooccurences of names of two researchers and calculates the streangth of the relation between them. Then we label the relation by analyzing the Web pages in which these two names cooccur. Research on social network extraction using search engines as ours, is attracting attention in Japan as well as abroad. However, the former approaches issue too many queries to search engines to extract a large-scale network. In this paper, we propose a method to filter superfluous queries and facilitates the extraction of large-scale networks. By this method we are able to extract a network of around 3000-nodes. Our experimental results show that the proposed method reduces the number of queries significantly while preserving the quality of the network as compared to former methods.

  3. Pharmacogenetics, pharmacogenomics and ayurgenomics for personalized medicine: a paradigm shift.

    PubMed

    Gupta, Pooja D

    2015-01-01

    The value of health care can be increased tremendously through individualized medicine. With the promise of individualized medicine, healthcare professionals will be able to better predict disease risk, prevent development of disease and manage treatments more efficiently thereby allowing people to be healthier and active longer. The developments in the area of pharmacogenetics/pharmacogenomics can help the physicians achieve the target of personalized medicine. Personalized medicine will come to mean not just the right drug for the right individual, but the right drug for the specific disease affecting a specific individual. The use of personalized medicine will make clinical trials more efficient by lowering the costs that would arise due to adverse drug effects and prescription of drugs that have been proven ineffective in certain genotypes. The genotypic experiments have laid valuable insights into genetic underpinnings of diseases. However it is being realized that identification of sub-groups within normal controls corresponding to contrasting disease susceptibility could lead to more effective discovery of predictive markers for diseases. However there are no modern methods available to look at the inter-individual differences within ethnically matched healthy populations. Ayurveda, an exquisitely elaborate system of predictive medicine which has been practiced for over 3500 years in India, can help in bridging this gap. In contrast to the contemporary system of medicine, the therapeutic regimen in Ayurveda is implicated on tridoshas and prakriti. According to this system, every individual is born with his or her own basic constitution, which to a great extent regulates inter-individual variability in susceptibility to diseases and response to external environment, diet and drugs. Thus the researchers in India have demonstrated that integration of this stratified approach of Ayurveda into genomics i.e. Ayurgenomics could complement personalized medicine

  4. Acceptance of Asthma Pharmacogenetic Study by Children and Adults

    PubMed Central

    Wu, Ann Chen; Davis, Robert; Tantisira, Kelan; Dutta-Linn, M. Maya; Hemmes, Mia; Weiss, Scott T.

    2012-01-01

    Background Pharmacogenetic testing may change clinical medicine by allowing clinicians to tailor medications based on a patient’s genetic makeup, however, these tests must first be validated in large, real-life populations of subjects that include children. A dearth of knowledge exists for whether pediatric populations are as willing as adult populations to provide samples for such studies. Objective (1) To assess whether pediatric and adult patients with persistent asthma are willing to provide specimens for DNA extraction and genetic studies. (2) To assess whether patients’ willingness to provide blood as compared to buccal smear specimens differ. Methods Of 644 patients ages 4–38 years who had three or more prescription fills for inhaled corticosteroids in one year, 60% (385) were randomized to the blood specimen group and 40% (259) were randomized to the buccal smear group in order to study acceptance of different biospecimen collection methods. Research assistants contacted subjects to obtain consent, perform a phone survey, and request a specimen. Results There were no baseline differences between subjects randomized to the blood specimen group versus buccal smear group with respect to age, gender, or number of dispensings of inhaled corticosteroids. Of 259 subjects in the buccal smear group, 30% (78) provided samples, and of 385 subjects in the blood specimen group, 16% (60) provided samples. Subjects randomized to the buccal smear group were more likely to provide specimens for genetic study compared to subjects randomized to the blood specimen group (RR 1.21; 95% CI 1.10 – 1.32), even after adjusting for age. Pediatric subjects were more likely to provide specimens for genetic study than adult subjects with 23% (113) of pediatric subjects providing samples and 15% (25) of adult subjects providing samples (p=0.03). Conclusion Children with asthma are as likely to participate in genetic studies as adults. Both children and adult subjects are more

  5. Pharmacogenetics, pharmacogenomics and ayurgenomics for personalized medicine: a paradigm shift.

    PubMed

    Gupta, Pooja D

    2015-01-01

    The value of health care can be increased tremendously through individualized medicine. With the promise of individualized medicine, healthcare professionals will be able to better predict disease risk, prevent development of disease and manage treatments more efficiently thereby allowing people to be healthier and active longer. The developments in the area of pharmacogenetics/pharmacogenomics can help the physicians achieve the target of personalized medicine. Personalized medicine will come to mean not just the right drug for the right individual, but the right drug for the specific disease affecting a specific individual. The use of personalized medicine will make clinical trials more efficient by lowering the costs that would arise due to adverse drug effects and prescription of drugs that have been proven ineffective in certain genotypes. The genotypic experiments have laid valuable insights into genetic underpinnings of diseases. However it is being realized that identification of sub-groups within normal controls corresponding to contrasting disease susceptibility could lead to more effective discovery of predictive markers for diseases. However there are no modern methods available to look at the inter-individual differences within ethnically matched healthy populations. Ayurveda, an exquisitely elaborate system of predictive medicine which has been practiced for over 3500 years in India, can help in bridging this gap. In contrast to the contemporary system of medicine, the therapeutic regimen in Ayurveda is implicated on tridoshas and prakriti. According to this system, every individual is born with his or her own basic constitution, which to a great extent regulates inter-individual variability in susceptibility to diseases and response to external environment, diet and drugs. Thus the researchers in India have demonstrated that integration of this stratified approach of Ayurveda into genomics i.e. Ayurgenomics could complement personalized medicine.

  6. Praxis-based research networks: an emerging paradigm for research that is rigorous, relevant and inclusive

    PubMed Central

    Werner, James J.; Stange, Kurt C.

    2016-01-01

    Practice-based research networks (PBRNs) have developed a grounded approach to conducting practice-relevant and translational research in community practice settings. Seismic shifts in the healthcare landscape are shaping PBRNs that work across organizational and institutional margins to address complex problems. Praxis-based research networks combine PBRN knowledge generation with multi-stakeholder learning, experimentation, and practical knowledge application. The catalytic processes in praxis-based research networks are cycles of action and reflection based on experience, observation, conceptualization, and experimentation by network members and partners. To facilitate co-learning and solution-building, these networks have a flexible architecture that allows pragmatic inclusion of stakeholders based on demands of the problem and the needs of the network. Praxis-based research networks represent an evolving trend that combines the core values of PBRNs with new opportunities for relevance, rigor, and broad participation. PMID:25381067

  7. Ocean Research - Perspectives from an international Ocean Research Coordination Network

    NASA Astrophysics Data System (ADS)

    Pearlman, Jay; Williams, Albert, III

    2013-04-01

    The need for improved coordination in ocean observations is more urgent now given the issues of climate change, sustainable food sources and increased need for energy. Ocean researchers must work across disciplines to provide policy makers with clear and understandable assessments of the state of the ocean. With advances in technology, not only in observation, but also communication and computer science, we are in a new era where we can answer questions asked over the last 100 years at the time and space scales that are relevant. Programs like GLOBEC moved us forward but we are still challenged by the disciplinary divide. Interdisciplinary problem solving must be addressed not only by the exchange of data between the many sides, but through levels where questions require day-to-day collaboration. A National Science Foundation-funded Research Coordination Network (RCN) is addressing approaches for improving interdisciplinary research capabilities in the ocean sciences. During the last year, the RCN had a working group for Open Data led by John Orcutt, Peter Pissierssens and Albert Williams III. The teams has focused on three areas: 1. Data and Information formats and standards; 2. Data access models (including IPR, business models for open data, data policies,...); 3. Data publishing, data citation. There has been a significant trend toward free and open access to data in the last few years. In 2007, the US announced that Landsat data would be available at no charge. Float data from the US (NDBC), JCOMM and OceanSites offer web-based access. The IODE is developing its Ocean Data Portal giving immediate and free access to ocean data. However, from the aspect of long-term collaborations across communities, this global trend is less robust than might appear at the surface. While there are many standard data formats for data exchange, there is not yet widespread uniformity in their adoption. Use of standard data formats can be encouraged in several ways: sponsors of

  8. From Human Genetics and Genomics to Pharmacogenetics and Pharmacogenomics: Past Lessons, Future Directions

    PubMed Central

    Nebert, Daniel W.; Zhang, Ge; Vesell, Elliot S.

    2009-01-01

    A brief history of human genetics and genomics is provided, comparing recent progress in those fields with that in pharmacogenetics and pharmacogenomics, which are subsets of genetics and genomics, respectively. Sequencing of the entire human genome, the mapping of common haplotypes of single-nucleotide polymorphisms (SNPs), and cost-effective genotyping technologies leading to genome-wide association (GWA) studies—have combined convincingly in the past several years to demonstrate the requirements needed to separate true associations from the plethora of false positives. While research in human genetics has moved from monogenic to oligogenic to complex diseases, its pharmacogenetics branch has followed, usually a few years behind. The continuous discoveries, even today, of new surprises about our genome cause us to question reviews declaring that “personalized medicine is almost here” or that “individualized drug therapy will soon be a reality.” As summarized herein, numerous reasons exist to show that an “unequivocal genotype” or even an “unequivocal phenotype” is virtually impossible to achieve in current limited-size studies of human populations. This problem (of insufficiently stringent criteria) leads to a decrease in statistical power and, consequently, equivocal interpretation of most genotype-phenotype association studies. It remains unclear whether personalized medicine or individualized drug therapy will ever be achievable by means of DNA testing alone. PMID:18464043

  9. Identifying emerging research collaborations and networks: Method development

    PubMed Central

    Dozier, Ann M.; Martina, Camille A.; O’Dell, Nicole L.; Fogg, Thomas T.; Lurie, Stephen J.; Rubinstein, Eric P.; Pearson, Thomas A.

    2014-01-01

    Clinical and translational research is a multidisciplinary, collaborative team process. To evaluate this process, we developed a method to document emerging research networks and collaborations in our medical center to describe their productivity and viability over time. Using an email survey, sent to 1,620 clinical and basic science full-and part-time faculty members, respondents identified their research collaborators. Initial analyses, using Pajek software, assessed the feasibility of using social network analysis (SNA) methods with these data. Nearly 400 respondents identified 1,594 collaborators across 28 medical center departments resulting in 309 networks with 5 or more collaborators. This low-burden approach yielded a rich dataset useful for evaluation using SNA to: a) assess networks at several levels of the organization, including intrapersonal (individuals), interpersonal (social), organizational/institutional leadership (tenure and promotion), and physical/environmental (spatial proximity) and b) link with other data to assess the evolution of these networks. PMID:24019209

  10. Identifying emerging research collaborations and networks: method development.

    PubMed

    Dozier, Ann M; Martina, Camille A; O'Dell, Nicole L; Fogg, Thomas T; Lurie, Stephen J; Rubinstein, Eric P; Pearson, Thomas A

    2014-03-01

    Clinical and translational research is a multidisciplinary, collaborative team process. To evaluate this process, we developed a method to document emerging research networks and collaborations in our medical center to describe their productivity and viability over time. Using an e-mail survey, sent to 1,620 clinical and basic science full- and part-time faculty members, respondents identified their research collaborators. Initial analyses, using Pajek software, assessed the feasibility of using social network analysis (SNA) methods with these data. Nearly 400 respondents identified 1,594 collaborators across 28 medical center departments resulting in 309 networks with 5 or more collaborators. This low-burden approach yielded a rich data set useful for evaluation using SNA to: (a) assess networks at several levels of the organization, including intrapersonal (individuals), interpersonal (social), organizational/institutional leadership (tenure and promotion), and physical/environmental (spatial proximity) and (b) link with other data to assess the evolution of these networks.

  11. Multipath routing in wireless sensor networks: survey and research challenges.

    PubMed

    Radi, Marjan; Dezfouli, Behnam; Abu Bakar, Kamalrulnizam; Lee, Malrey

    2012-01-01

    A wireless sensor network is a large collection of sensor nodes with limited power supply and constrained computational capability. Due to the restricted communication range and high density of sensor nodes, packet forwarding in sensor networks is usually performed through multi-hop data transmission. Therefore, routing in wireless sensor networks has been considered an important field of research over the past decade. Nowadays, multipath routing approach is widely used in wireless sensor networks to improve network performance through efficient utilization of available network resources. Accordingly, the main aim of this survey is to present the concept of the multipath routing approach and its fundamental challenges, as well as the basic motivations for utilizing this technique in wireless sensor networks. In addition, we present a comprehensive taxonomy on the existing multipath routing protocols, which are especially designed for wireless sensor networks. We highlight the primary motivation behind the development of each protocol category and explain the operation of different protocols in detail, with emphasis on their advantages and disadvantages. Furthermore, this paper compares and summarizes the state-of-the-art multipath routing techniques from the network application point of view. Finally, we identify open issues for further research in the development of multipath routing protocols for wireless sensor networks.

  12. Multipath Routing in Wireless Sensor Networks: Survey and Research Challenges

    PubMed Central

    Radi, Marjan; Dezfouli, Behnam; Bakar, Kamalrulnizam Abu; Lee, Malrey

    2012-01-01

    A wireless sensor network is a large collection of sensor nodes with limited power supply and constrained computational capability. Due to the restricted communication range and high density of sensor nodes, packet forwarding in sensor networks is usually performed through multi-hop data transmission. Therefore, routing in wireless sensor networks has been considered an important field of research over the past decade. Nowadays, multipath routing approach is widely used in wireless sensor networks to improve network performance through efficient utilization of available network resources. Accordingly, the main aim of this survey is to present the concept of the multipath routing approach and its fundamental challenges, as well as the basic motivations for utilizing this technique in wireless sensor networks. In addition, we present a comprehensive taxonomy on the existing multipath routing protocols, which are especially designed for wireless sensor networks. We highlight the primary motivation behind the development of each protocol category and explain the operation of different protocols in detail, with emphasis on their advantages and disadvantages. Furthermore, this paper compares and summarizes the state-of-the-art multipath routing techniques from the network application point of view. Finally, we identify open issues for further research in the development of multipath routing protocols for wireless sensor networks. PMID:22368490

  13. Learning Networks--Enabling Change through Community Action Research

    ERIC Educational Resources Information Center

    Bleach, Josephine

    2016-01-01

    Learning networks are a critical element of ethos of the community action research approach taken by the Early Learning Initiative at the National College of Ireland, a community-based educational initiative in the Dublin Docklands. Key criteria for networking, whether at local, national or international level, are the individual's and…

  14. The future of intersite networking. [Office of Energy Research

    SciTech Connect

    Not Available

    1986-11-01

    Copies of viewgraphs and summaries of three discussion groups are presented. The purpose of the workshop was to identify strategies for meeting the computer networking needs to the scientists under the Office of Energy Research. (WRF)

  15. Unravelling the Social Network: Theory and Research

    ERIC Educational Resources Information Center

    Merchant, Guy

    2012-01-01

    Despite the widespread popularity of social networking sites (SNSs) amongst children and young people in compulsory education, relatively little scholarly work has explored the fundamental issues at stake. This paper makes an original contribution to the field by locating the study of this online activity within the broader terrain of social…

  16. 75 FR 80853 - Designing a Digital Future: Federally Funded Research and Development in Networking and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ... Designing a Digital Future: Federally Funded Research and Development in Networking and Information Technology AGENCY: National Coordination Office (NCO) for the Networking and Information Technology Research... ``Designing a Digital Future: Federally Funded Research and Development in Networking and...

  17. Research Universities as Knowledge Networks: The Role of Institutional Research

    ERIC Educational Resources Information Center

    Chirikov, Igor

    2013-01-01

    This article focuses on the elaboration of institutional research practice, which is an important element of any research university. The study addresses three questions. First, how did institutional research arise, and what is its raison d'etre in a research university? Second, how can institutional research contribute to the improvement of…

  18. Direct2Experts: a pilot national network to demonstrate interoperability among research-networking platforms

    PubMed Central

    Barnett, William; Conlon, Mike; Eichmann, David; Kibbe, Warren; Falk-Krzesinski, Holly; Halaas, Michael; Johnson, Layne; Meeks, Eric; Mitchell, Donald; Schleyer, Titus; Stallings, Sarah; Warden, Michael; Kahlon, Maninder

    2011-01-01

    Research-networking tools use data-mining and social networking to enable expertise discovery, matchmaking and collaboration, which are important facets of team science and translational research. Several commercial and academic platforms have been built, and many institutions have deployed these products to help their investigators find local collaborators. Recent studies, though, have shown the growing importance of multiuniversity teams in science. Unfortunately, the lack of a standard data-exchange model and resistance of universities to share information about their faculty have presented barriers to forming an institutionally supported national network. This case report describes an initiative, which, in only 6 months, achieved interoperability among seven major research-networking products at 28 universities by taking an approach that focused on addressing institutional concerns and encouraging their participation. With this necessary groundwork in place, the second phase of this effort can begin, which will expand the network's functionality and focus on the end users. PMID:22037890

  19. Direct2Experts: a pilot national network to demonstrate interoperability among research-networking platforms.

    PubMed

    Weber, Griffin M; Barnett, William; Conlon, Mike; Eichmann, David; Kibbe, Warren; Falk-Krzesinski, Holly; Halaas, Michael; Johnson, Layne; Meeks, Eric; Mitchell, Donald; Schleyer, Titus; Stallings, Sarah; Warden, Michael; Kahlon, Maninder

    2011-12-01

    Research-networking tools use data-mining and social networking to enable expertise discovery, matchmaking and collaboration, which are important facets of team science and translational research. Several commercial and academic platforms have been built, and many institutions have deployed these products to help their investigators find local collaborators. Recent studies, though, have shown the growing importance of multiuniversity teams in science. Unfortunately, the lack of a standard data-exchange model and resistance of universities to share information about their faculty have presented barriers to forming an institutionally supported national network. This case report describes an initiative, which, in only 6 months, achieved interoperability among seven major research-networking products at 28 universities by taking an approach that focused on addressing institutional concerns and encouraging their participation. With this necessary groundwork in place, the second phase of this effort can begin, which will expand the network's functionality and focus on the end users. PMID:22037890

  20. Direct2Experts: a pilot national network to demonstrate interoperability among research-networking platforms.

    PubMed

    Weber, Griffin M; Barnett, William; Conlon, Mike; Eichmann, David; Kibbe, Warren; Falk-Krzesinski, Holly; Halaas, Michael; Johnson, Layne; Meeks, Eric; Mitchell, Donald; Schleyer, Titus; Stallings, Sarah; Warden, Michael; Kahlon, Maninder

    2011-12-01

    Research-networking tools use data-mining and social networking to enable expertise discovery, matchmaking and collaboration, which are important facets of team science and translational research. Several commercial and academic platforms have been built, and many institutions have deployed these products to help their investigators find local collaborators. Recent studies, though, have shown the growing importance of multiuniversity teams in science. Unfortunately, the lack of a standard data-exchange model and resistance of universities to share information about their faculty have presented barriers to forming an institutionally supported national network. This case report describes an initiative, which, in only 6 months, achieved interoperability among seven major research-networking products at 28 universities by taking an approach that focused on addressing institutional concerns and encouraging their participation. With this necessary groundwork in place, the second phase of this effort can begin, which will expand the network's functionality and focus on the end users.

  1. Comparison of Delivery Strategies for Pharmacogenetic Testing Services

    PubMed Central

    Moaddeb, Jivan

    2013-01-01

    The number and use of pharmacogenetic tests to assess a patient’s likelihood of response or risk of an adverse event is expanding across medical specialties and becoming more prevalent. During this period of development and translation, different approaches are being investigated to optimize delivery of pharmacogenetic services. In this paper, we review preemptive and point-of-care delivery approaches currently implemented or being investigated and discuss the advantages and disadvantages of each approach. The continued growth in knowledge about the genetic basis of drug response combined with development of new and cheaper testing technologies and electronic medical records will impact future delivery systems. Regardless of delivery approach, the currently limited knowledge of health professionals about genetics generally or PGx specifically will remain a major obstacle to utilization. PMID:24384556

  2. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy?

    PubMed Central

    Roco, Ángela; Cayún, Juan; Contreras, Stephania; Stojanova, Jana; Quiñones, Luis

    2014-01-01

    Several recent pharmacogenetic studies have investigated the variability in both outcome and toxicity in cisplatin-based therapies. These studies have focused on the genetic variability of therapeutic targets that could affect cisplatin response and toxicity in diverse type of cancer including lung, gastric, ovarian, testicular, and esophageal cancer. In this review, we seek to update the reader in this area of investigation, focusing primarily on DNA reparation enzymes and cisplatin metabolism through Glutathione S-Transferases (GSTs). Current evidence indicates a potential application of pharmacogenetics in therapeutic schemes in which cisplatin is the cornerstone of these treatments. Therefore, a collaborative effort is required to study these molecular characteristics in order to generate a genetic panel with clinical utility. PMID:25452763

  3. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions

    PubMed Central

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

  4. Pharmacogenetics of chemotherapy-induced nausea and vomiting.

    PubMed

    Sugino, Shigekazu; Janicki, Piotr K

    2015-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with distressing adverse effects observed in patients during cytotoxic chemotherapy. One of the potential factors explaining suboptimal response to currently used antiemetics is variability in genes encoding enzymes and proteins that play a role in the action of antiemetic drugs. Pharmacogenomics studies of CINV are sparse and focus mainly on polymorphisms associated with serotonin receptor, drug metabolism and drug transport. Currently, the role of pharmacogenetics in mechanisms of CINV has not been fully unraveled, and it is premature to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice. More uniform studies, with genetic profiles and biomarkers relevant for the proposed target and transporter mechanisms, are needed.

  5. Pharmacogenetics of ribavirin-induced anemia in hepatitis C.

    PubMed

    Ampuero, Javier; Romero-Gómez, Manuel

    2016-09-01

    Pharmacogenetics assesses inherited genetic differences in drug metabolic pathways and its role in medicine is growing. Ribavirin (RBV) and peginterferon were the standard of care therapy in hepatitis C virus infection during 15 years, with the addition of first-generation protease inhibitors at the beginning of 2010s. New direct-acting agents are the new standard of care, but RBV remains important in some scenarios. The main adverse effect of RBV is anemia, which requires dose reduction and even stopping treatment in some patients. Pharmacogenetics has identified ITPA and SLC28/29 genes to be closely related to RBV-induced anemia. The routine evaluation of these genes could help to identify those patients at risk of developing anemia during the hepatitis C virus treatment. PMID:27547881

  6. [The usefulness of pharmacogenetics for a more individualized treatment. The example thiopurines in inflammatory bowel disease and childhood leukemia].

    PubMed

    Lindqvist Appell, Malin; Mårtensson, Lars-Göran; Almer, Sven; Peterson, Curt

    2015-06-30

    Thiopurines are chemotherapeutic drugs used for treatment of inflammatory bowel diseases and childhood leukemia. Thiopurine methyltransferase (TPMT) is a polymorphic enzyme involved in the metabolism of thiopurines. Individuals lacking TPMT are at increased risk for severe side effects when treated with conventional doses of thiopurines. A research group at the division of drug research at Linköping University is studying thiopurine pharmacogenetics. Since the year 2000, the lab has determined the TPMT status in over 12000 individuals, as an aid to decide thiopurine doses before starting treatment. New knowledge of how genetic factors influence thiopurine treatment effect are anticipated to improve the possibilities for individualization of thiopurine therapy.

  7. Pharmacogenetic studies of epilepsy drugs: are we there yet?

    PubMed

    Spurr, Nigel K

    2006-05-01

    One of the mantras of scientists working in the field of pharmacogenetics is 'the right dose for the right patient'. A recent article has gone someway towards demonstrating that this goal can be achieved using genetic approaches. It is one of the first reports to show that a specific polymorphism can predict the maximum tolerated dose of two anti-epileptic drugs. However, further studies are necessary to validate these observations.

  8. Pharmacogenetic studies update in type 2 diabetes mellitus.

    PubMed

    Singh, Shalini; Usman, Kauser; Banerjee, Monisha

    2016-08-10

    Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment. PMID:27555891

  9. Pharmacogenetic studies update in type 2 diabetes mellitus

    PubMed Central

    Singh, Shalini; Usman, Kauser; Banerjee, Monisha

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment. PMID:27555891

  10. Pharmacogenetics: Using Genetic Information to Guide Drug Therapy

    PubMed Central

    CHANG, KU-LANG; WEITZEL, KRISTIN; SCHMIDT, SIEGFRIED

    2016-01-01

    Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects. PMID:26447442

  11. Pharmacogenetics: Using Genetic Information to Guide Drug Therapy.

    PubMed

    Chang, Ku-Lang; Weitzel, Kristin; Schmidt, Siegfried

    2015-10-01

    Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.

  12. Pharmacogenetics: Using Genetic Information to Guide Drug Therapy.

    PubMed

    Chang, Ku-Lang; Weitzel, Kristin; Schmidt, Siegfried

    2015-10-01

    Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects. PMID:26447442

  13. Measuring Networking as an Outcome Variable in Undergraduate Research Experiences

    PubMed Central

    Hanauer, David I.; Hatfull, Graham

    2015-01-01

    The aim of this paper is to propose, present, and validate a simple survey instrument to measure student conversational networking. The tool consists of five items that cover personal and professional social networks, and its basic principle is the self-reporting of degrees of conversation, with a range of specific discussion partners. The networking instrument was validated in three studies. The basic psychometric characteristics of the scales were established by conducting a factor analysis and evaluating internal consistency using Cronbach’s alpha. The second study used a known-groups comparison and involved comparing outcomes for networking scales between two different undergraduate laboratory courses (one involving a specific effort to enhance networking). The final study looked at potential relationships between specific networking items and the established psychosocial variable of project ownership through a series of binary logistic regressions. Overall, the data from the three studies indicate that the networking scales have high internal consistency (α = 0.88), consist of a unitary dimension, can significantly differentiate between research experiences with low and high networking designs, and are related to project ownership scales. The ramifications of the networking instrument for student retention, the enhancement of public scientific literacy, and the differentiation of laboratory courses are discussed. PMID:26538387

  14. Measuring Networking as an Outcome Variable in Undergraduate Research Experiences.

    PubMed

    Hanauer, David I; Hatfull, Graham

    2015-01-01

    The aim of this paper is to propose, present, and validate a simple survey instrument to measure student conversational networking. The tool consists of five items that cover personal and professional social networks, and its basic principle is the self-reporting of degrees of conversation, with a range of specific discussion partners. The networking instrument was validated in three studies. The basic psychometric characteristics of the scales were established by conducting a factor analysis and evaluating internal consistency using Cronbach's alpha. The second study used a known-groups comparison and involved comparing outcomes for networking scales between two different undergraduate laboratory courses (one involving a specific effort to enhance networking). The final study looked at potential relationships between specific networking items and the established psychosocial variable of project ownership through a series of binary logistic regressions. Overall, the data from the three studies indicate that the networking scales have high internal consistency (α = 0.88), consist of a unitary dimension, can significantly differentiate between research experiences with low and high networking designs, and are related to project ownership scales. The ramifications of the networking instrument for student retention, the enhancement of public scientific literacy, and the differentiation of laboratory courses are discussed. PMID:26538387

  15. Measuring Networking as an Outcome Variable in Undergraduate Research Experiences.

    PubMed

    Hanauer, David I; Hatfull, Graham

    2015-01-01

    The aim of this paper is to propose, present, and validate a simple survey instrument to measure student conversational networking. The tool consists of five items that cover personal and professional social networks, and its basic principle is the self-reporting of degrees of conversation, with a range of specific discussion partners. The networking instrument was validated in three studies. The basic psychometric characteristics of the scales were established by conducting a factor analysis and evaluating internal consistency using Cronbach's alpha. The second study used a known-groups comparison and involved comparing outcomes for networking scales between two different undergraduate laboratory courses (one involving a specific effort to enhance networking). The final study looked at potential relationships between specific networking items and the established psychosocial variable of project ownership through a series of binary logistic regressions. Overall, the data from the three studies indicate that the networking scales have high internal consistency (α = 0.88), consist of a unitary dimension, can significantly differentiate between research experiences with low and high networking designs, and are related to project ownership scales. The ramifications of the networking instrument for student retention, the enhancement of public scientific literacy, and the differentiation of laboratory courses are discussed.

  16. Latin American Lidar Network (LALINET) for aerosol research: Diagnosis on network instrumentation

    NASA Astrophysics Data System (ADS)

    Guerrero-Rascado, Juan Luis; Landulfo, Eduardo; Antuña, Juan Carlos; de Melo Jorge Barbosa, Henrique; Barja, Boris; Bastidas, Álvaro Efrain; Bedoya, Andrés Esteban; da Costa, Renata Facundes; Estevan, René; Forno, Ricardo; Gouveia, Diego Alvés; Jiménez, Cristofer; Larroza, Eliane Gonçalves; da Silva Lopes, Fábio Juliano; Montilla-Rosero, Elena; Arruda Moreira, Gregori de; Nakaema, Walker Morinobu; Nisperuza, Daniel; Alegria, Dairo; Múnera, Mauricio; Otero, Lidia; Papandrea, Sebastián; Pallota, Juan Vicente; Pawelko, Ezequiel; Quel, Eduardo Jaime; Ristori, Pablo; Rodrigues, Patricia Ferrini; Salvador, Jacobo; Sánchez, Maria Fernanda; Silva, Antonieta

    2016-02-01

    LALINET (Latin American Lidar Network), previously known as ALINE, is the first fully operative lidar network for aerosol research in South America, probing the atmosphere on regular basis since September 2013. The general purpose of this network is to attempt to fill the gap in the knowledge on aerosol vertical distribution over South America and its direct and indirect impact on weather and climate by the establishment of a vertically-resolved dataset of aerosol properties. Similarly to other lidar research networks, most of the LALINET instruments are not commercially produced and, consequently, configurations, capabilities and derived-products can be remarkably different among stations. It is a fact that such un-biased 4D dataset calls for a strict standardization from the instrumental and data processing point of view. This study has been envisaged to investigate the ongoing network configurations with the aim of highlighting the instrumental strengths and weaknesses of LALINET.

  17. The Mind Research Network - Mental Illness Neuroscience Discovery Grant

    SciTech Connect

    Roberts, J.; Calhoun, V.

    2013-12-17

    The scientific and technological programs of the Mind Research Network (MRN), reflect DOE missions in basic science and associated instrumentation, computational modeling, and experimental techniques. MRN's technical goals over the course of this project have been to develop and apply integrated, multi-modality functional imaging techniques derived from a decade of DOE-support research and technology development.

  18. Networks of Practice in Science Education Research: A Global Context

    ERIC Educational Resources Information Center

    Martin, Sonya N.; Siry, Christina

    2011-01-01

    In this paper, we employ cultural sociology and Braj Kachru's model of World Englishes as theoretical and analytical tools for considering English as a form of capital necessary for widely disseminating research findings from local networks of practice to the greater science education research community. We present a brief analysis of recent…

  19. Non-US artificial neural network research. FASAC special study

    SciTech Connect

    Davidson, R. B.

    1991-10-01

    This assessment was undertaken to examine for US Government research and development sponsors (and for Government policy-makers and analysts who must be aware of foreign scientific and technological capabilities) the recent range, quality, and accomplishments of non-US artificial neural network research and development activities. It records the project's initial assessments of major artificial neural network research and development activities in Western Europe, Japan, and the Soviet Union, where the largest, most organized efforts are proceeding or where potential military applications are of interest to US policy-makers. We plan to issue updated versions of this report periodically, as more research and development activities (in more places) are examined and as the efforts assessed in this report succeed or fail. This report focuses on artificial neural networks as an information processing technology, the goal of which is design and production of powerful computers for appropriate applications.

  20. EEG-based research on brain functional networks in cognition.

    PubMed

    Wang, Niannian; Zhang, Li; Liu, Guozhong

    2015-01-01

    Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders. PMID:26405867

  1. Network of participants in European research: accepted versus rejected proposals

    NASA Astrophysics Data System (ADS)

    Tsouchnika, Maria; Argyrakis, Panos

    2014-12-01

    We investigate the network formed by the collaboration of researchers seeking funding by the European Commission by submitting research proposals. Institutions are network nodes and collaborations are links between the nodes. We constructed one network for the accepted proposals and one for the rejected ones, in order to look for any structural differences between them. To this end, first, we compare the size of the largest connected components and the resulting degree distributions. The latter show notable difference only in the region of relatively small degrees. We calculate the assortative mixing by participant type, i.e. a property which indicates whether the participant is a university/research institute, a company (non-profit included), or undefined. By aggregating the data of both networks into three geographical scales (city, region, country), we compare the degree assortativity and average node weight, in all scales. With respect to these two features the networks display similar behaviour. Finally, we compare a series of centrality measures and the Minimum Spanning Trees, at the country scale, to assess the relative performance of the countries. We find that five countries, France, Germany, the United Kingdom, Spain and Italy, play a central role in both networks, however, their relative significance is not the same.

  2. Research, Supervision, and the Network Society

    ERIC Educational Resources Information Center

    Dennison, Carmel

    2009-01-01

    Much has been written about the use of information and communication technology (ICT) in distance learning environments. A quick Google search turns up as many as 178,000 links to the term. ICT has been less used and discussed as a means of communication between research student and supervisor--particularly where this is the major means of student…

  3. Defining and measuring successful emergency care networks: a research agenda.

    PubMed

    Glickman, Seth W; Kit Delgado, M; Hirshon, Jon Mark; Hollander, Judd E; Iwashyna, Theodore J; Jacobs, Alice K; Kilaru, Austin S; Lorch, Scott A; Mutter, Ryan L; Myers, Sage R; Owens, Pamela L; Phelan, Michael P; Pines, Jesse M; Seymour, Christopher W; Ewen Wang, N; Branas, Charles C

    2010-12-01

    The demands on emergency services have grown relentlessly, and the Institute of Medicine (IOM) has asserted the need for "regionalized, coordinated, and accountable emergency care systems throughout the country." There are large gaps in the evidence base needed to fix the problem of how emergency care is organized and delivered, and science is urgently needed to define and measure success in the emerging network of emergency care. In 2010, Academic Emergency Medicine convened a consensus conference entitled "Beyond Regionalization: Integrated Networks of Emergency Care." This article is a product of the conference breakout session on "Defining and Measuring Successful Networks"; it explores the concept of integrated emergency care delivery and prioritizes a research agenda for how to best define and measure successful networks of emergency care. The authors discuss five key areas: 1) the fundamental metrics that are needed to measure networks across time-sensitive and non-time-sensitive conditions; 2) how networks can be scalable and nimble and can be creative in terms of best practices; 3) the potential unintended consequences of networks of emergency care; 4) the development of large-scale, yet feasible, network data systems; and 5) the linkage of data systems across the disease course. These knowledge gaps must be filled to improve the quality and efficiency of emergency care and to fulfill the IOM's vision of regionalized, coordinated, and accountable emergency care systems.

  4. What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

    PubMed

    de Leon, Jose; Spina, Edoardo

    2016-01-01

    This editorial considers two questions in psychopharmacotherapy: 1) What is needed to market pharmacogenetic tests in the US, since the US appears to lead other countries? and 2) What is needed for US-marketed pharmacogenetic tests to be incorporated by prescribers into long-term practice? US marketing of pharmacogenetic tests requires 1) understanding the pharmacological complexity of drug response, 2) modifying the oversight of non-FDA regulatory agencies, 3) clarifying the FDA's role and 4) promoting innovative marketing. The incorporation of pharmacogenetic tests into long-term practice requires 1) not jeopardizing pharmacogenetic testing by short-sighted marketing of non-validated tests, 2) educating prescribers about benefits, 3) educating patients about limitations and 4) considering the differences between isolated testing and generalized testing incorporating big data. PMID:26580456

  5. What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

    PubMed

    de Leon, Jose; Spina, Edoardo

    2016-01-01

    This editorial considers two questions in psychopharmacotherapy: 1) What is needed to market pharmacogenetic tests in the US, since the US appears to lead other countries? and 2) What is needed for US-marketed pharmacogenetic tests to be incorporated by prescribers into long-term practice? US marketing of pharmacogenetic tests requires 1) understanding the pharmacological complexity of drug response, 2) modifying the oversight of non-FDA regulatory agencies, 3) clarifying the FDA's role and 4) promoting innovative marketing. The incorporation of pharmacogenetic tests into long-term practice requires 1) not jeopardizing pharmacogenetic testing by short-sighted marketing of non-validated tests, 2) educating prescribers about benefits, 3) educating patients about limitations and 4) considering the differences between isolated testing and generalized testing incorporating big data.

  6. US computer research networks: Current and future

    NASA Technical Reports Server (NTRS)

    Kratochvil, D.; Sood, D.; Verostko, A.

    1989-01-01

    During the last decade, NASA LeRC's Communication Program has conducted a series of telecommunications forecasting studies to project trends and requirements and to identify critical telecommunications technologies that must be developed to meet future requirements. The Government Networks Division of Contel Federal Systems has assisted NASA in these studies, and the current study builds upon these earlier efforts. The current major thrust of the NASA Communications Program is aimed at developing the high risk, advanced, communications satellite and terminal technologies required to significantly increase the capacity of future communications systems. Also, major new technological, economic, and social-political events and trends are now shaping the communications industry of the future. Therefore, a re-examination of future telecommunications needs and requirements is necessary to enable NASA to make management decisions in its Communications Program and to ensure the proper technologies and systems are addressed. This study, through a series of Task Orders, is helping NASA define the likely communication service needs and requirements of the future and thereby ensuring that the most appropriate technology developments are pursued.

  7. The Emerging Role of Admixture in the Pharmacogenetics of Puerto Rican Hispanics

    PubMed Central

    Duconge, Jorge; Ruaño, Gualberto

    2011-01-01

    Admixture is of great relevance to the clinical application of pharmacogenetics and personalized medicine. Preliminary findings in Puerto Ricans further substantiate the argument for admixture as a critical covariate in a customized DNA-guided warfarin dosing algorithm. To this purpose, a genome-wide approach that incorporates admixture as an independent predictor of dose variability in DNA-guided algorithms has been postulated. Admixture is expected to be able to reveal some relevant associations in the genetic epidemiology of Hispanics and will be indispensable to assure that pharmacogenomic research can be pursued in such mixed populations. Consequently, the clinical utility of knowing an individual’s genotype before initiating drug treatment in Puerto Ricans, and Hispanics in general, will finally be untangled by developing a “Genetic Prescription Model” that takes admixture into consideration. This approach will help lead physicians and patients to their desired treatment goal, resulting in more effective healthcare in admixed people. PMID:23227441

  8. Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians.

    PubMed

    Zai, Gwyneth; Brandl, Eva J; Müller, Daniel J; Richter, Margaret A; Kennedy, James L

    2014-06-01

    Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder with high genetic influence. Antidepressants such as serotonin reuptake inhibitors, are widely accepted as the first-line medications for OCD; however, approximately 50% of OCD patients show poor response. Personalized medicine utilizing genetic testing has recently received much attention because the variability of antidepressant response and tolerability are partly due to an individual's genetic variations. This has led to researchers investigating the role of specific genetic factors on antidepressant response and utility of testing in the clinical realm. Genetic test panels are showing promise for guiding antidepressant treatment to improve outcomes in depression. This article will review the most recent findings in the pharmacogenetics of OCD and its related disorders. Promising results have been reported for several serotonergic and glutamatergic system genes and the cytochrome CYP450 liver enzyme genes, which appear to play an important role in OCD and antidepressant response.

  9. Pharmacogenetics and pharmacogenomics of sexual dysfunction: current status, gaps and potential applications.

    PubMed

    Abdel-Hamid, Ibrahim A; Andersson, Karl-Erik

    2009-10-01

    Although treatment of different types of sexual dysfunction has improved in the past decade with the introduction of phosphodiesterase type 5 inhibitors and selective serotonin reuptake inhibitors, response rates to these targeted therapies are variable. There are a number of studies in the published literature that provide proof-of-concept that genetic variation contributes to the variable response. Pharmacogenomics will most likely be one part of our therapeutic armamentarium in the future and will provide a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution. This article will review English language medical literature on the state-of-the-art genetic polymorphisms of drug targets, transporters and signaling molecules as well as pharmacogenetic studies of sexual dysfunction and suggested possible applications. Collectively, the data demonstrate that pharmacogenomics in the field of sexual medicine is still in its infancy. More research will provide further intriguing new discoveries in years to come.

  10. Stories in Networks and Networks in Stories: A Tri-Modal Model for Mixed-Methods Social Network Research on Teachers

    ERIC Educational Resources Information Center

    Baker-Doyle, Kira J.

    2015-01-01

    Social network research on teachers and schools has risen exponentially in recent years as an innovative method to reveal the role of social networks in education. However, scholars are still exploring ways to incorporate traditional quantitative methods of Social Network Analysis (SNA) with qualitative approaches to social network research. This…

  11. The Long Term Agroecosystem Research Network - Shared research strategy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture faces tremendous challenges in meeting multiple societal goals, including a safe and plentiful food supply; climate change adaptation and mitigation; supplying sources of bioenergy; improving water, air, and soil quality; and maintaining biodiversity. The Long Term Agroecosystem Research...

  12. AmeriFlux Measurement Network: Science Team Research

    SciTech Connect

    Law, B E

    2012-12-12

    Research involves analysis and field direction of AmeriFlux operations, and the PI provides scientific leadership of the AmeriFlux network. Activities include the coordination and quality assurance of measurements across AmeriFlux network sites, synthesis of results across the network, organizing and supporting the annual Science Team Meeting, and communicating AmeriFlux results to the scientific community and other users. Objectives of measurement research include (i) coordination of flux and biometric measurement protocols (ii) timely data delivery to the Carbon Dioxide Information and Analysis Center (CDIAC); and (iii) assurance of data quality of flux and ecosystem measurements contributed by AmeriFlux sites. Objectives of integration and synthesis activities include (i) integration of site data into network-wide synthesis products; and (ii) participation in the analysis, modeling and interpretation of network data products. Communications objectives include (i) organizing an annual meeting of AmeriFlux investigators for reporting annual flux measurements and exchanging scientific information on ecosystem carbon budgets; (ii) developing focused topics for analysis and publication; and (iii) developing data reporting protocols in support of AmeriFlux network goals.

  13. Research on the complex network of the UNSPSC ontology

    NASA Astrophysics Data System (ADS)

    Xu, Yingying; Zou, Shengrong; Gu, Aihua; Wei, Li; Zhou, Ta

    The UNSPSC ontology mainly applies to the classification system of the e-business and governments buying the worldwide products and services, and supports the logic structure of classification of the products and services. In this paper, the related technologies of the complex network were applied to analyzing the structure of the ontology. The concept of the ontology was corresponding to the node of the complex network, and the relationship of the ontology concept was corresponding to the edge of the complex network. With existing methods of analysis and performance indicators in the complex network, analyzing the degree distribution and community of the ontology, and the research will help evaluate the concept of the ontology, classify the concept of the ontology and improve the efficiency of semantic matching.

  14. Promoting Cognitive Health: A Formative Research Collaboration of the Healthy Aging Research Network

    ERIC Educational Resources Information Center

    Laditka, James N.; Beard, Renee L.; Bryant, Lucinda L.; Fetterman, David; Hunter, Rebecca; Ivey, Susan; Logsdon, Rebecca G.; Sharkey, Joseph R.; Wu, Bei

    2009-01-01

    Purpose: Evidence suggests that healthy lifestyles may help maintain cognitive health. The Prevention Research Centers Healthy Aging Research Network, 9 universities collaborating with their communities and the Centers for Disease Control and Prevention, is conducting a multiyear research project, begun in 2005, to understand how to translate this…

  15. Patient-powered research networks aim to improve patient care and health research.

    PubMed

    Fleurence, Rachael L; Beal, Anne C; Sheridan, Susan E; Johnson, Lorraine B; Selby, Joe V

    2014-07-01

    The era of big data, loosely defined as the development and analysis of large or complex data sets, brings new opportunities to empower patients and their families to generate, collect, and use their health information for both clinical and research purposes. In 2013 the Patient-Centered Outcomes Research Institute launched a large national research network, PCORnet, that includes both clinical and patient-powered research networks. This article describes these networks, their potential uses, and the challenges they face. The networks are engaging patients, family members, and caregivers in four key ways: contributing data securely, with privacy protected; including diverse and representative groups of patients in research; prioritizing research questions, participating in research, and disseminating results; and participating in the leadership and governance of patient-powered research networks. If technical, regulatory, and organizational challenges can be overcome, PCORnet will allow research to be conducted more efficiently and cost-effectively and results to be disseminated quickly back to patients, clinicians, and delivery systems to improve patient health. PMID:25006148

  16. Patient-powered research networks aim to improve patient care and health research.

    PubMed

    Fleurence, Rachael L; Beal, Anne C; Sheridan, Susan E; Johnson, Lorraine B; Selby, Joe V

    2014-07-01

    The era of big data, loosely defined as the development and analysis of large or complex data sets, brings new opportunities to empower patients and their families to generate, collect, and use their health information for both clinical and research purposes. In 2013 the Patient-Centered Outcomes Research Institute launched a large national research network, PCORnet, that includes both clinical and patient-powered research networks. This article describes these networks, their potential uses, and the challenges they face. The networks are engaging patients, family members, and caregivers in four key ways: contributing data securely, with privacy protected; including diverse and representative groups of patients in research; prioritizing research questions, participating in research, and disseminating results; and participating in the leadership and governance of patient-powered research networks. If technical, regulatory, and organizational challenges can be overcome, PCORnet will allow research to be conducted more efficiently and cost-effectively and results to be disseminated quickly back to patients, clinicians, and delivery systems to improve patient health.

  17. The Adoption of Alcohol Pharmacotherapies in the Clinical Trials Network: The Influence of Research Network Participation

    PubMed Central

    Abraham, Amanda J.; Knudsen, Hannah K.; Rothrauff, Tanja C.; Roman, Paul M.

    2010-01-01

    Organizational participation in clinical research may lead to adoption of the intervention by treatment agencies, but it is not known whether research involvement enhances innovativeness beyond the specific interventions that are tested. The National Institute on Drug Abuse’s (NIDA) Clinical Trial Network (CTN) is a platform for considering this research question. To date, the CTN has not conducted research on medications for alcohol use disorders (AUDs), so greater adoption of innovative AUD pharmacotherapies by CTN-affiliated programs would suggest an added value of research network participation. Using longitudinal data from a pooled sample of CTN and non-CTN publicly funded treatment programs, we investigate adoption of tablet naltrexone and acamprosate over a two-year period. CTN-affiliated programs were more likely to have adopted tablet naltrexone and acamprosate at 24-month follow-up, net of the effects of a range of organizational characteristics. Research network participation may thus enhance organizational innovativeness to include interventions beyond the scope of the network. PMID:20117908

  18. Leadership in complex networks: the importance of network position and strategic action in a translational cancer research network

    PubMed Central

    2013-01-01

    Background Leadership behaviour in complex networks is under-researched, and little has been written concerning leadership of translational research networks (TRNs) that take discoveries made ‘at the bench’ and translate them into practices used ‘at the bedside.’ Understanding leaders’ opportunities and behaviours within TRNs working to solve this key problem in implementing evidence into clinical practice is therefore important. This study explored the network position of governing body members and perceptions of their role in a new TRN in Sydney, Australia. The paper asks three questions: Firstly, do the formal, mandated leaders of this TRN hold key positions of centrality or brokerage in the informal social network of collaborative ties? Secondly, if so, do they recognise the leadership opportunities that their network positions afford them? Thirdly, what activities associated with these key roles do they believe will maximise the TRN’s success? Methods Semi-structured interviews of all 14 governing body members conducted in early 2012 explored perceptions of their roles and sought comments on a list of activities drawn from review of successful transdisciplinary collaboratives combined with central and brokerage roles. An on-line, whole network survey of all 68 TRN members sought to understand and map existing collaborative connections. Leaders’ positions in the network were assessed using UCInet, and graphs were generated in NetDraw. Results Social network analysis identified that governing body members had high centrality and high brokerage potential in the informal network of work-related ties. Interviews showed perceived challenges including ‘silos’ and the mismatch between academic and clinical goals of research. Governing body members recognised their central positions, which would facilitate the leadership roles of leading, making decisions, and providing expert advice necessary for the co-ordination of effort and relevant input across

  19. Infrastructure Requirements for Practice-Based Research Networks

    PubMed Central

    Green, Lee A.; White, Linda L.; Barry, Henry C.; Nease, Donald E.; Hudson, Brenda L.

    2005-01-01

    BACKGROUND The practice-based research network (PBRN) is the basic laboratory for primary care research. Although most PBRNs include some common elements, their infrastructures vary widely. We offer suggestions for developing and supporting infrastructures to enhance PBRN research success. METHODS Information was compiled based on published articles, the PBRN Resource Center survey of 2003, our PBRN experiences, and discussions with directors and coordinators from other PBRNs. RESULTS PBRN research ranges from observational studies, through intervention studies, clinical trials, and quality of care research, to large-scale practice change interventions. Basic infrastructure elements such as a membership roster, a board, a director, a coordinator, a news-sharing function, a means of addressing requirements of institutional review boards and the Health Insurance Portability and Accountability Act, and a network meeting must exist to support these initiatives. Desirable elements such as support staff, electronic medical records, multiuser databases, mentoring and development programs, mock study sections, and research training are costly and difficult to sustain through project grant funds. These infrastructure elements must be selected, configured, and sized according to the PBRN’s self-defined research mission. Annual infrastructure costs are estimated to range from $69,700 for a basic network to $287,600 for a moderately complex network. CONCLUSIONS Well-designed and properly supported PBRN infrastructures can support a wide range of research of great direct value to patients and society. Increased and more consistent infrastructure support could generate an explosion of pragmatic, generalizable knowledge about currently understudied populations, settings, and health care problems. PMID:15928219

  20. The Georgia Psychoeducational Network (GPN) Research Report, 1988.

    ERIC Educational Resources Information Center

    Swan, William W., Ed.; Brown, Carvin L., Ed.

    1988-01-01

    This research report contains seven papers on students with serious Emotional Disturbances (SED) and/or Severe Behavior Disorder (SBD) who participated in the Georgia Psychoeducational Network Program (GPN). "The 1982 Cohort of GPN Preschoolers--Where Are They in 1987-1988?" (Juanda Ponsell and others) reports the placement of 75 preschoolers with…

  1. Artificial Neural Networks in Policy Research: A Current Assessment.

    ERIC Educational Resources Information Center

    Woelfel, Joseph

    1993-01-01

    Suggests that artificial neural networks (ANNs) exhibit properties that promise usefulness for policy researchers. Notes that ANNs have found extensive use in areas once reserved for multivariate statistical programs such as regression and multiple classification analysis and are developing an extensive community of advocates for processing text…

  2. Higher Education Change and Social Networks: A Review of Research

    ERIC Educational Resources Information Center

    Kezar, Adrianna

    2014-01-01

    This article reviews literature on the potential for understanding higher education change processes through social network analysis (SNA). In this article, the main tenets of SNA are reviewed and, in conjunction with organizational theory, are applied to higher education change to develop a set of hypotheses that can be tested in future research.

  3. Water resources: Research network to track alpine water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The water cycle in alpine environments worldwide supplies fresh water to vast downstream areas inhabited by more than half of humanity. The International Network for Alpine Research Catchment Hydrology (INARCH) was launched this year by the Global Energy and Water Exchanges project of the World Clim...

  4. Exploration of Heterogeneity in Distributed Research Network Drug Safety Analyses

    ERIC Educational Resources Information Center

    Hansen, Richard A.; Zeng, Peng; Ryan, Patrick; Gao, Juan; Sonawane, Kalyani; Teeter, Benjamin; Westrich, Kimberly; Dubois, Robert W.

    2014-01-01

    Distributed data networks representing large diverse populations are an expanding focus of drug safety research. However, interpreting results is difficult when treatment effect estimates vary across datasets (i.e., heterogeneity). In a previous study, risk estimates were generated for selected drugs and potential adverse outcomes. Analyses were…

  5. Using Action Research to Investigate Social Networking Technologies

    ERIC Educational Resources Information Center

    Worrall, Lisa; Harris, Katy

    2013-01-01

    This article outlines the first cycle of an Action Research (AR) investigation into why professional learners are not using the Social Networking Technologies (SNTs) of their bespoke website. It presents the rationale of how this study came about, the ontological and epistemological stance of the authors and how this led to the particular choice…

  6. EARLINET: potential operationality of a research network

    NASA Astrophysics Data System (ADS)

    Sicard, M.; D'Amico, G.; Comerón, A.; Mona, L.; Alados-Arboledas, L.; Amodeo, A.; Baars, H.; Belegante, L.; Binietoglou, I.; Bravo-Aranda, J. A.; Fernández, A. J.; Fréville, P.; García-Vizcaíno, D.; Giunta, A.; Granados-Muñoz, M. J.; Guerrero-Rascado, J. L.; Hadjimitsis, D.; Haefele, A.; Hervo, M.; Iarlori, M.; Kokkalis, P.; Lange, D.; Mamouri, R. E.; Mattis, I.; Molero, F.; Montoux, N.; Muñoz, A.; Muñoz Porcar, C.; Navas-Guzmán, F.; Nicolae, D.; Nisantzi, A.; Papagiannopoulos, N.; Papayannis, A.; Pereira, S.; Preißler, J.; Pujadas, M.; Rizi, V.; Rocadenbosch, F.; Sellegri, K.; Simeonov, V.; Tsaknakis, G.; Wagner, F.; Pappalardo, G.

    2015-07-01

    In the framework of ACTRIS summer 2012 measurement campaign (8 June-17 July 2012), EARLINET organized and performed a controlled exercise of feasibility to demonstrate its potential to perform operational, coordinated measurements and deliver products in near-real time. Eleven lidar stations participated to the exercise which started on 9 July 2012 at 06:00 UT and ended 72 h later on 12 July at 06:00 UT. For the first time the Single-Calculus Chain (SCC), the common calculus chain developed within EARLINET for the automatic evaluation of lidar data from raw signals up to the final products, was used. All stations sent in real time measurements of 1 h of duration to the SCC server in a predefined netcdf file format. The pre-processing of the data was performed in real time by the SCC while the optical processing was performed in near-real time after the exercise ended. 98 and 84 % of the files sent to SCC were successfully pre-processed and processed, respectively. Those percentages are quite large taking into account that no cloud screening was performed on lidar data. The paper shows time series of continuous and homogeneously obtained products retrieved at different levels of the SCC: range-square corrected signals (pre-processing) and daytime backscatter and nighttime extinction coefficient profiles (optical processing), as well as combined plots of all direct and derived optical products. The derived products include backscatter- and extinction-related Ångström exponents, lidar ratios and color ratios. The combined plots reveal extremely valuable for aerosol classification. The efforts made to define the measurements protocol and to configure properly the SCC pave the way for applying this protocol for specific applications such as the monitoring of special events, atmospheric modelling, climate research and calibration/validation activities of spaceborne observations.

  7. PG4KDS: A Model for the Clinical Implementation of Pre-emptive Pharmacogenetics

    PubMed Central

    Hoffman, James M.; Haidar, Cyrine E.; Wilkinson, Mark R.; Crews, Kristine R.; Baker, Donald K.; Kornegay, Nancy M.; Yang, Wenjian; Pui, Ching-Hon; Reiss, Ulrike M.; Gaur, Aditya H.; Howard, Scott C.; Evans, William E.; Broeckel, Ulrich; Relling, Mary V.

    2014-01-01

    Pharmacogenetics is frequently cited as an area for initial focus of the clinical implementation of genomics. Through the PG4KDS protocol, St. Jude Children’s Research Hospital pre-emptively genotypes patients for 230 genes using the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array supplemented with a CYP2D6 copy number assay. The PG4KDS protocol provides a rational, stepwise process for implementing gene/drug pairs, organizing data, and obtaining consent from patients and families. Through August 2013, 1559 patients have been enrolled, and 4 gene tests have been released into the electronic health record (EHR) for clinical implementation: TPMT, CYP2D6, SLCO1B1, and CYP2C19. These genes are coupled to 12 high-risk drugs. Of the 1016 patients with genotype test results available, 78% of them had at least one high-risk (i.e., actionable) genotype result placed in their EHR. Each diplotype result released to the EHR is coupled with an interpretive consult that is created in a concise, standardized format. To support-gene based prescribing at the point of care, 55 interruptive clinical decision support (CDS) alerts were developed. Patients are informed of their genotyping result and its relevance to their medication use through a letter. Key elements necessary for our successful implementation have included strong institutional support, a knowledgeable clinical laboratory, a process to manage any incidental findings, a strategy to educate clinicians and patients, a process to return results, and extensive use of informatics, especially CDS. Our approach to pre-emptive clinical pharmacogenetics has proven feasible, clinically useful, and scalable. PMID:24619595

  8. Interdependent networks - Topological percolation research and application in finance

    NASA Astrophysics Data System (ADS)

    Zhou, Di

    This dissertation covers the two major parts of my Ph.D. research: i) developing a theoretical framework of complex networks and applying simulation and numerical methods to study the robustness of the network system, and ii) applying statistical physics concepts and methods to quantitatively analyze complex systems and applying the theoretical framework to study real-world systems. In part I, we focus on developing theories of interdependent networks as well as building computer simulation models, which includes three parts: 1) We report on the effects of topology on failure propagation for a model system consisting of two interdependent networks. We find that the internal node correlations in each of the networks significantly changes the critical density of failures, which can trigger the total disruption of the two-network system. Specifically, we find that the assortativity within a single network decreases the robustness of the entire system. 2) We study the percolation behavior of two interdependent scale-free (SF) networks under random failure of 1-p fraction of nodes. We find that as the coupling strength q between the two networks reduces from 1 (fully coupled) to 0 (no coupling), there exist two critical coupling strengths q1 and q2 , which separate the behaviors of the giant component as a function of p into three different regions, and for q2 < q < q 1 , we observe a hybrid order phase transition phenomenon. 3) We study the robustness of n interdependent networks with partially support-dependent relationship both analytically and numerically. We study a starlike network of n Erdos-Renyi (ER), SF networks and a looplike network of n ER networks, and we find for starlike networks, their phase transition regions change with n, but for looplike networks the phase regions change with average degree k . In part II, we apply concepts and methods developed in statistical physics to study economic systems. We analyze stock market indices and foreign exchange

  9. The Use and Significance of a Research Networking System

    PubMed Central

    Yuan, Leslie; Daigre, John; Meeks, Eric; Nelson, Katie; Piontkowski, Cynthia; Reuter, Katja; Sak, Rachael; Turner, Brian; Weber, Griffin M; Chatterjee, Anirvan

    2014-01-01

    Background Universities have begun deploying public Internet systems that allow for easy search of their experts, expertise, and intellectual networks. Deployed first in biomedical schools but now being implemented more broadly, the initial motivator of these research networking systems was to enable easier identification of collaborators and enable the development of teams for research. Objective The intent of the study was to provide the first description of the usage of an institutional research “social networking” system or research networking system (RNS). Methods Number of visits, visitor location and type, referral source, depth of visit, search terms, and click paths were derived from 2.5 years of Web analytics data. Feedback from a pop-up survey presented to users over 15 months was summarized. Results RNSs automatically generate and display profiles and networks of researchers. Within 2.5 years, the RNS at the University of California, San Francisco (UCSF) achieved one-seventh of the monthly visit rate of the main longstanding university website, with an increasing trend. Visitors came from diverse locations beyond the institution. Close to 75% (74.78%, 208,304/278,570) came via a public search engine and 84.0% (210 out of a sample of 250) of these queried an individual’s name that took them directly to the relevant profile page. In addition, 20.90% (214 of 1024) visits went beyond the page related to a person of interest to explore related researchers and topics through the novel and networked information provided by the tool. At the end of the period analyzed, more than 2000 visits per month traversed 5 or more links into related people and topics. One-third of visits came from returning visitors who were significantly more likely to continue to explore networked people and topics (P<.001). Responses to an online survey suggest a broad range of benefits of using the RNS in supporting the research and clinical mission. Conclusions Returning

  10. Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

    PubMed

    Xu, Hang; Su, Shi; Tang, Wuji; Wei, Meng; Wang, Tao; Wang, Dongjin; Ge, Weihong

    2015-09-01

    A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase.

  11. Exploring Knowledge Processes Based on Teacher Research in a School-University Research Network of a Master's Program

    ERIC Educational Resources Information Center

    Cornelissen, Frank; van Swet, Jacqueline; Beijaard, Douwe; Bergen, Theo

    2013-01-01

    School-university research networks aim at closer integration of research and practice by means of teacher research. Such practice-oriented research can benefit both schools and universities. This paper reports on a multiple-case study of five participants in a school-university research network in a Dutch master's program. The research question…

  12. Social Networking and Online Recruiting for HIV Research: Ethical Challenges

    PubMed Central

    Curtis, Brenda L.

    2015-01-01

    Social networking sites and online advertising organizations provide HIV/AIDS researchers access to target populations, often reaching difficult-to-reach populations. However, this benefit to researchers raises many issues for the protections of prospective research participants. Traditional recruitment procedures have involved straightforward transactions between the researchers and prospective participants; online recruitment is a more complex and indirect form of communication involving many parties engaged in the collecting, aggregating, and storing of research participant data. Thus, increased access to online data has challenged the adequacy of current and established procedures for participants’ protections, such as informed consent and privacy/confidentiality. Internet-based HIV/AIDS research recruitment and its ethical challenges are described, and research participant safeguards and best practices are outlined. PMID:24572084

  13. New Zealand needs a Practice Based Research Network.

    PubMed

    Leitch, Sharon

    2016-03-01

    Practice Based Research Networks (PBRNs) are groups of general practices collaborating to produce research. Contemporary New Zealand health information technology systems are ideal for electronic data extraction for PBRN research. Stakeholders have a valuable, but typically underutilised, part to play in research. Development of an e-participation platform will facilitate stakeholder engagement. New Zealand is in a unique position to create an innovative, low cost, stakeholder-engaged PBRN. This type of PBRN would offer unparalleled research opportunities, and would strengthen New Zealand's general practice research capacity. The more research information we have based on our New Zealand population, the more appropriate care we can provide. Establishing a stakeholder-engaged PBRN in New Zealand will promote and support transformational change within our health system. PMID:27477369

  14. Social networking and online recruiting for HIV research: ethical challenges.

    PubMed

    Curtis, Brenda L

    2014-02-01

    Social networking sites and online advertising organizations provide HIV/AIDS researchers access to target populations, often reaching difficult-to-reach populations. However, this benefit to researchers raises many issues for the protections of prospective research participants. Traditional recruitment procedures have involved straightforward transactions between the researchers and prospective participants; online recruitment is a more complex and indirect form of communication involving many parties engaged in the collecting, aggregating, and storing of research participant data. Thus, increased access to online data has challenged the adequacy of current and established procedures for participants' protections, such as informed consent and privacy/confidentiality. Internet-based HIV/AIDS research recruitment and its ethical challenges are described, and research participant safeguards and best practices are outlined.

  15. New Zealand needs a Practice Based Research Network.

    PubMed

    Leitch, Sharon

    2016-03-01

    Practice Based Research Networks (PBRNs) are groups of general practices collaborating to produce research. Contemporary New Zealand health information technology systems are ideal for electronic data extraction for PBRN research. Stakeholders have a valuable, but typically underutilised, part to play in research. Development of an e-participation platform will facilitate stakeholder engagement. New Zealand is in a unique position to create an innovative, low cost, stakeholder-engaged PBRN. This type of PBRN would offer unparalleled research opportunities, and would strengthen New Zealand's general practice research capacity. The more research information we have based on our New Zealand population, the more appropriate care we can provide. Establishing a stakeholder-engaged PBRN in New Zealand will promote and support transformational change within our health system.

  16. Social networking and online recruiting for HIV research: ethical challenges.

    PubMed

    Curtis, Brenda L

    2014-02-01

    Social networking sites and online advertising organizations provide HIV/AIDS researchers access to target populations, often reaching difficult-to-reach populations. However, this benefit to researchers raises many issues for the protections of prospective research participants. Traditional recruitment procedures have involved straightforward transactions between the researchers and prospective participants; online recruitment is a more complex and indirect form of communication involving many parties engaged in the collecting, aggregating, and storing of research participant data. Thus, increased access to online data has challenged the adequacy of current and established procedures for participants' protections, such as informed consent and privacy/confidentiality. Internet-based HIV/AIDS research recruitment and its ethical challenges are described, and research participant safeguards and best practices are outlined. PMID:24572084

  17. Pharmacogenetics in cancer chemotherapy: balancing toxicity and response.

    PubMed

    Donnelly, James G

    2004-04-01

    The goal of chemotherapy is the elimination of tumor cells from the host. This is achieved by the use of therapeutic agents that are often more harmful to normal tissues than to the targeted tumor. Many chemotherapeutic agents are designed to damage cell replication machinery either directly at the level of DNA or indirectly, by inhibiting enzymes involved with DNA repair and synthesis. Novel therapeutic agents that exert their effects at signal transduction pathways have advanced chemotherapy; however, a role for the classic chemotherapeutic agents remains. These classic agents are associated with tumor cell resistance, toxicity, and occasionally secondary neoplasia. Current practices for the dosing of therapeutic agents rely on height and body surface measurements or drug monitoring and Bayesian adaptive control. Pharmacogenetics is emerging as an alternate approach to managing chemotherapy that may prevent undertreatment while avoiding overtreatment and associated toxicities. By determining the polymorphic genetic makeup of the host and, in some instances, the altered genetic expression of the tumor, chemotherapy can be tailored for interindividual response and toxicity avoidance. Chemotherapy is particularly applicable to the pharmacogenetic approach to tailored therapy for a number of reasons. The margin of safety is low with chemotherapeutic agents. Some drugs require biotransformation for activation. Drug activation correlates with toxicity. The pathways of drug clearance or inactivation exhibit polymorphic differences. Interindividual, race-specific, and age-related responses to chemotherapeutic agents are common. Last, drug resistance can be inherent to the tumor as a result of the suppression of apoptosis. Variations in response and toxicity to a specific drug can be caused by alterations in drug-metabolizing enzymes or receptor expression. These effects can be classed as pharmacokinetic and pharmacogenetic differences. Some of the genes known to display

  18. [Pharmacogenetics--implications for health management and health care economics].

    PubMed

    Weihrauch, Thomas R

    2002-07-15

    Pharmacogenetics, which is principally concerned with drug efficacy and safety, will change the way future health care is practiced. The growing understanding of the genetic basis for drug response and use of this knowledge to predict the response of an individual patient offer new opportunities to meet the changing needs of health care systems and the demands placed upon them. For the individual patient, overall quality of life should be higher as physicians will be able to select the most effective and safest treatments for them. However, the cost of patient evaluation will need to be weighed against the additional therapeutic benefit and savings made by avoidance of unnecessary and inadequate drug use and adverse drug responses. Getting the right medicine at the right dose to the patient first time and avoidance of "try and see" prescribing also have the potential to reduce costs due a reduction in number of visits to the physician required to obtain satisfactory treatment. Application of pharmacogenetics to drug development has the potential to streamline the drug development process. Disease and therapy differentiation may lead to stratification of patient groups, and it is possible that the fragmented indications will not represent commercially attractive markets to the pharmaceutical industry with current marketing paradigms. However, the ability to target patients more accurately may represent considerable commercial value within a given market sector. Changes in health care policy and structure will be needed so that short-term budget constraints are not allowed to take precedence over mid- to long-term benefits. In order to realize the potential of pharmacogenetics, tailored communication/education programs for the key stakeholders--patients and patient groups, health care professionals, regulators, health care industry (biotechnology, pharmaceutical and diagnostic companies), health care payers, governments, and academia--will be necessary

  19. Research Trends in Wireless Visual Sensor Networks When Exploiting Prioritization

    PubMed Central

    Costa, Daniel G.; Guedes, Luiz Affonso; Vasques, Francisco; Portugal, Paulo

    2015-01-01

    The development of wireless sensor networks for control and monitoring functions has created a vibrant investigation scenario, where many critical topics, such as communication efficiency and energy consumption, have been investigated in the past few years. However, when sensors are endowed with low-power cameras for visual monitoring, a new scope of challenges is raised, demanding new research efforts. In this context, the resource-constrained nature of sensor nodes has demanded the use of prioritization approaches as a practical mechanism to lower the transmission burden of visual data over wireless sensor networks. Many works in recent years have considered local-level prioritization parameters to enhance the overall performance of those networks, but global-level policies can potentially achieve better results in terms of visual monitoring efficiency. In this paper, we make a broad review of some recent works on priority-based optimizations in wireless visual sensor networks. Moreover, we envisage some research trends when exploiting prioritization, potentially fostering the development of promising optimizations for wireless sensor networks composed of visual sensors. PMID:25599425

  20. Enabling research in care homes: an evaluation of a national network of research ready care homes

    PubMed Central

    2014-01-01

    Background In the UK care homes are one of the main providers of long term care for older people with dementia. Despite the recent increase in care home research, residents with dementia are often excluded from studies. Care home research networks have been recommended by the Ministerial Advisory Group on Dementia Research (MAGDR) as a way of increasing research opportunities for residents with dementia. This paper reports on an evaluation of the feasibility and early impact of an initiative to increase care home participation in research. Methods A two phase, mixed methods approach was used; phase 1 established a baseline of current and recent studies including the National Institute for Health Research portfolio. To explore the experiences of recruiting care homes and research participation, interviews were conducted with researchers working for the Dementia and Neurodegenerative Diseases Research Network (DeNDRoN) and care home managers. In phase 2, four DeNDRoN area offices recruited care homes to a care home network for their region. The care home networks were separate from the DeNDRoN research network. Diaries were used to document and cost recruitment; DeNDRoN staff were interviewed to understand the barriers, facilitators and impact of the care home networks. Results Thirty three current or recent studies were identified as involving care homes as care home specific studies or those which included residents. Further details of care home recruitment were obtained on 20 studies by contacting study teams. Care home managers were keen to be involved in research that provided staff support, benefits for residents and with minimal disruption. In phase 2, 141 care homes were recruited to the care home research networks, through corporate engagement and individual invitation. Pre-existing relationships with care homes facilitated recruitment. Sites with minimal experience of working with care homes identified the need for care home training for researchers

  1. Issue network versus producer network? ASH, the Tobacco Products Research Trust and UK smoking policy.

    PubMed

    Berridge, Virginia

    2005-01-01

    Policy science studies of networks in smoking policy segment the smoking arena into a "producer network" of industrial and retail interests and an "issue network" of anti-smoking organisations. Case studies of ASH (Action on Smoking and Health) and the Tobacco Products Research Trust (TPRT) indicate that networks in smoking policy were more complex and overlapping. ASH pioneered a new style of media-conscious health activism in the 1970s with an anti-industry line. Nevertheless the strategy of harm reduction remained an objective for industry and government, and also for some public health interests through the work of the TPRT. First safer smoking and then nicotine were the focus of these activities.

  2. Research and development of network virtual instrument laboratory

    NASA Astrophysics Data System (ADS)

    Cui, Hongmei; Pei, Xichun; Ma, Hongyue; Ma, Shuoshi

    2006-11-01

    A software platform of the network virtual instrument test laboratory has been developed to realize the network function of the test and signal analysis as well as the share of the hardware based on the data transmission theory and the study of the present technologies of the network virtual instrument. The whole design procedure was also presented in this paper. The main work of the research is as follows. 1. A suitable scheme of the test system with B/S mode and the virtual instrument laboratory with BSDA (Browser/Server/Database/Application) mode was determined. 2. The functions were classified and integrated by adopting the multilayer structure. The application for the virtual instruments running in the client terminal and the network management server managing the multiuser in the test laboratory according to the "Concurrent receival, sequential implementation" strategy in Java as well as the code of the test server application responding the client's requests of test and signal analysis in LabWindows/CVI were developed. As the extending part of network function of the original virtual test and analysis instruments, a software platform of network virtual instrument test laboratory was built as well. 3. The communication of the network data between Java and the LabWindows/CVI was realized. 4. The database was imported to store the data as well as the correlative information acquired by the server and help the network management server to manage the multiuser in the test laboratory. 5. A website embedding Java Applet of virtual instrument laboratory with the on-line help files was designed.

  3. Research on Application of Neural Networks in Organizational Management

    NASA Astrophysics Data System (ADS)

    Marinescu, Simona-Ioana

    2014-12-01

    Since there is no clear definition of the terms "neural network" and "neuronal network", this paper is aimed primarily to establish the difference between them by a range of comparative research. Using a chart, the three parts that make up the structure of a neuron will be compared with the structure of an organization to determine who does in terms of role, in order to reproduce the neuron in the structuring level of an organization and give a meaning to the term of "organizational neuron."

  4. A global spacecraft control network for spacecraft autonomy research

    NASA Technical Reports Server (NTRS)

    Kitts, Christopher A.

    1996-01-01

    The development and implementation of the Automated Space System Experimental Testbed (ASSET) space operations and control network, is reported on. This network will serve as a command and control architecture for spacecraft operations and will offer a real testbed for the application and validation of advanced autonomous spacecraft operations strategies. The proposed network will initially consist of globally distributed amateur radio ground stations at locations throughout North America and Europe. These stations will be linked via Internet to various control centers. The Stanford (CA) control center will be capable of human and computer based decision making for the coordination of user experiments, resource scheduling and fault management. The project's system architecture is described together with its proposed use as a command and control system, its value as a testbed for spacecraft autonomy research, and its current implementation.

  5. [Research on Zhejiang blood information network and management system].

    PubMed

    Yan, Li-Xing; Xu, Yan; Meng, Zhong-Hua; Kong, Chang-Hong; Wang, Jian-Min; Jin, Zhen-Liang; Wu, Shi-Ding; Chen, Chang-Shui; Luo, Ling-Fei

    2007-02-01

    This research was aimed to develop the first level blood information centralized database and real time communication network at a province area in China. Multiple technology like local area network database separate operation, real time data concentration and distribution mechanism, allopatric backup, and optical fiber virtual private network (VPN) were used. As a result, the blood information centralized database and management system were successfully constructed, which covers all the Zhejiang province, and the real time exchange of blood data was realised. In conclusion, its implementation promote volunteer blood donation and ensure the blood safety in Zhejiang, especially strengthen the quick response to public health emergency. This project lays the first stone of centralized test and allotment among blood banks in Zhejiang, and can serve as a reference of contemporary blood bank information systems in China.

  6. Pharmacogenetics in Psychiatry: Are We Ready for Widespread Clinical Use?

    PubMed Central

    Arranz, Maria J.; Kapur, Shitij

    2008-01-01

    There are high expectations about the capabilities of pharmacogenetics to tailor psychotropic treatment and “personalize” treatment. While a large number of associations, with generally small effect size, have been discovered, a “test” with widespread use and adoption is still missing. A more realistic picture, recognizing the important contribution of clinical and environmental factors toward overall clinical outcome has emerged. In this emerging view, genetic findings, if considered individually, may have limited clinical applications. Thus, in recent years, combinations of information in several genes have been used for the selection of appropriate therapeutic doses and for the prediction of agranulocytosis, hyperlipidemia, and response to antipsychotic and antidepressant medications. While these tests based on multiple genes show greater predictive ability than individual allele tests, their net impact on clinical consequence and costs is limited, thus leading to limited penetration into widespread clinical use. As one looks at other branches of medicine, there are successful examples of pharmacogenetic tests guiding treatment, and thus, it is reasonable to hope that with the incorporation of clinical and environmental information and the identification of new genes drawn from genome-wide analysis, will improve the predictive utility of these tests leading to their increased use by clinicians. PMID:18753306

  7. Optimizing drug outcomes through pharmacogenetics: A case for preemptive genotyping

    PubMed Central

    Schildcrout, Jonathan S.; Denny, Joshua C.; Bowton, Erica; Gregg, William; Pulley, Jill M.; Basford, Melissa A.; Cowan, James D.; Xu, Hua; Ramirez, Andrea H.; Crawford, Dana C.; Ritchie, Marylyn D.; Peterson, Josh F.; Masys, Daniel R.; Wilke, Russell A.; Roden, Dan M.

    2013-01-01

    Routine integration of genotype data into drug decision-making could improve patient safety, particularly if many relevant genetic variants can be assayed simultaneously before target drug prescribing. The frequency of pharmacogenetic prescribing opportunities and the potential adverse events (AE) mitigated are unknown. We examined the frequency with which 56 medications with known outcomes influenced by variant alleles were prescribed in a cohort of 52,942 medical home patients at Vanderbilt University Medical Center. Within a five-year window, we estimated that 64.8% (95% CI: 64.4%-65.2%) of individuals were exposed to at least one medication with an established pharmacogenetic association. Using previously published results for six medications with well-characterized, severe genetically-linked AEs, we estimated that 398 events (95% CI, 225 - 583) could have been prevented with an effective preemptive genotyping program. Our results suggest that multiplexed, preemptive genotyping may represent an efficient alternative approach to current single use (“reactive”) methods and may improve safety. PMID:22739144

  8. Pharmacogenetics of antipsychotic treatment response and side effects

    PubMed Central

    Mackenzie, B; Souza, RP; Likhodi, O; Tiwari, AK; Zai, CC; Sturgess, J

    2011-01-01

    Antipsychotic drugs are particularly interesting in pharmacogenetic studies as they are associated with a large interindividual variability in terms of response and side effects and, therefore, frequently need to be discontinued, requiring switches to other antipsychotics. Any information that allows the prediction of outcome to a given antipsychotic in a particular patient will, therefore, be of great help for the clinician to minimize time and find the right drug for the right patient, thus optimizing response and minimizing side effects. This will also have a substantial impact on compliance and doctor–patient relationships. Moreover, antipsychotic drug treatments are often required for life-long treatment and are also frequently prescribed to the more ‘vulnerable’ populations: children, adolescents and the elderly. This article focuses on some important studies performed with candidate gene variants associated with antipsychotic response. In addition, important findings in pharmacogenetic studies of antipsychotic-induced side effects will be briefly summarized, such as antipsychotic treatment induced tardive dyskinesia and weight gain. PMID:22287936

  9. Challenges to Integrating Pharmacogenetic Testing into Medication Therapy Management

    PubMed Central

    Allen LaPointe, Nancy M.; Moaddeb, Jivan

    2015-01-01

    Background Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatment(s) to reduce risk of adverse responses and improve efficacy. PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify ineffective and/or harmful drugs or drug combinations. This “enhanced” MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing two key factors that impact patient adherence - concern and necessity. However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined. Objectives In this paper, we consider some of the challenges to the integration and delivery of PGx testing in MTM services. What is already known about this subject While the addition of pharmacogenetic testing has been suggested, little literature exists exploring the challenges or feasibility of doing so. PMID:25803768

  10. Online Social Networks and Smoking Cessation: A Scientific Research Agenda

    PubMed Central

    Graham, Amanda L; Byron, M. Justin; Niaura, Raymond S; Abrams, David B

    2011-01-01

    Background Smoking remains one of the most pressing public health problems in the United States and internationally. The concurrent evolution of the Internet, social network science, and online communities offers a potential target for high-yield interventions capable of shifting population-level smoking rates and substantially improving public health. Objective Our objective was to convene leading practitioners in relevant disciplines to develop the core of a strategic research agenda on online social networks and their use for smoking cessation, with implications for other health behaviors. Methods We conducted a 100-person, 2-day, multidisciplinary workshop in Washington, DC, USA. Participants worked in small groups to formulate research questions that could move the field forward. Discussions and resulting questions were synthesized by the workshop planning committee. Results We considered 34 questions in four categories (advancing theory, understanding fundamental mechanisms, intervention approaches, and evaluation) to be the most pressing. Conclusions Online social networks might facilitate smoking cessation in several ways. Identifying new theories, translating these into functional interventions, and evaluating the results will require a concerted transdisciplinary effort. This report presents a series of research questions to assist researchers, developers, and funders in the process of efficiently moving this field forward. PMID:22182518

  11. Practice Based Research Networks Impacting Periodontal Care: PEARL Initiative

    PubMed Central

    Curro, Frederick A.; Thompson, Van P.; Grill, Ashley; Vena, Don; Terracio, Louis; Naftolin, Frederick

    2014-01-01

    In 2005, the National Institute of Dental and Craniofacial Research /National Institutes of Health funded the largest initiative to date to affect change in the delivery of oral care. This commentary provides the background for the first study related to periodontics in a Practice Based Research Network (PBRN). It was conducted in the Practitioners Engaged in Applied Research & Learning (PEARL) Network. The PEARL Network is headquartered at New York University College of Dentistry. The basic tenet of the PBRN initiative is to engage clinicians to participate in clinical studies, where they will be more likely to accept the results and to incorporate the findings into their practices. This process may reduce the translational gap that exists between new findings and the time it takes for them to be incorporated into clinical practice. The cornerstone of the PBRN studies is to conduct comparative effectiveness research studies to disseminate findings to the profession and improve care. This is particularly important because the majority of dentists practice independently. Having practitioners generate clinical data allows them to contribute in the process of knowledge development and incorporate the results in their practice to assist in closing the translational gap. With the advent of electronic health systems on the horizon, dentistry may be brought into the mainstream health care paradigm and the PBRN concept can serve as the skeletal framework for advancing the profession provided there is consensus on the terminology used. PMID:22702516

  12. Undergraduate Research Experiences with the Global Telescope Network

    NASA Astrophysics Data System (ADS)

    McLin, Kevin M.; Wyman, K.; Broughton, N.; Coble, K.; Cominsky, L. R.

    2009-01-01

    Students at Chicago State University and Sonoma State University have undertaken observational programs using telescopes of the Global Telescope Network (GTN) and SkyNet. The GTN is a network of small telescopes funded by GLAST to support the science of high energy astrophysics missions, specifically GLAST, Swift and XMM-Newton. It is managed by the NASA E/PO Group at Sonoma State University. SkyNet encompasses a network  of small telescopes managed from the University of North Carolina to catch gamma ray burst afterglows. A primary motivator behind both networks is education. In the program outlined here, undergraduate students will schedule, reduce and analyze observations of active galaxies and other targets. Students will then present their work as part of observational course work, or in some cases as a "capstone” research experience required for graduation. This work will give the students direct experience with several aspects of scientific research, including literature searches, data acquisition and analysis, and reporting of results.

  13. Social Working Memory: Neurocognitive Networks and Directions for Future Research

    PubMed Central

    Meyer, Meghan L.; Lieberman, Matthew D.

    2012-01-01

    Navigating the social world requires the ability to maintain and manipulate information about people’s beliefs, traits, and mental states. We characterize this capacity as social working memory (SWM). To date, very little research has explored this phenomenon, in part because of the assumption that general working memory systems would support working memory for social information. Various lines of research, however, suggest that social cognitive processing relies on a neurocognitive network (i.e., the “mentalizing network”) that is functionally distinct from, and considered antagonistic with, the canonical working memory network. Here, we review evidence suggesting that demanding social cognition requires SWM and that both the mentalizing and canonical working memory neurocognitive networks support SWM. The neural data run counter to the common finding of parametric decreases in mentalizing regions as a function of working memory demand and suggest that the mentalizing network can support demanding cognition, when it is demanding social cognition. Implications for individual differences in social cognition and pathologies of social cognition are discussed. PMID:23267340

  14. Mapping collaboration networks in the world of Autism Research.

    PubMed

    Goldstein, Neal D; Tager-Flusberg, Helen; Lee, Brian K

    2015-02-01

    In the era of globalization and with the emergence of autism spectrum disorder as a global concern, the landscape of autism research has expanded to encompass much of the world. Here, we seek to provide an overview of the world of autism research, by documenting collaboration underlying the International Meeting for Autism Research (IMFAR), the pre-eminent annual scientific meeting devoted to the presentation of the latest autism research. We analyzed published abstracts presented at IMFAR meetings, between 2008 and 2013, to determine patterns of collaboration. We described collaboration networks on the individual, institutional, and international levels, and visually depicted these results on spatial network maps. Consistent with findings from other scientific disciplines, we found that collaboration is correlated with research productivity. Collaborative hotspots of autism research throughout the years were clustered on the East and West coasts of the U.S., Canada, and northern Europe. In years when conferences were held outside of North America, the proportion of abstracts from Europe and Asia increased. While IMFAR has traditionally been dominated by a large North American presence, greater global representation may be attained by shifting meeting locations to other regions of the world.

  15. Multispecies networks: visualizing the psychological research of the Committee for Research in Problems of Sex.

    PubMed

    Pettit, Michael; Serykh, Darya; Green, Christopher D

    2015-03-01

    In our current moment, there is considerable interest in networks, in how people and things are connected. This essay outlines one approach that brings together insights from actor-network theory, social network analysis, and digital history to interpret past scientific activity. Multispecies network analysis (MNA) is a means of understanding the historical interactions among scientists, institutions, and preferred experimental animals. A reexamination of studies of sexual behavior funded by the Committee for Research in Problems of Sex between the 1920s and the 1940s demonstrates the applicability of MNA to clarifying the relations that sustained this area of psychology. The measures of weighted degree and betweenness can highlight which nodes (whether organisms or institutions) were particularly "central" to this network. Rats featured as the animals most widely studied during this period, but the analysis also reveals distinct institutional and disciplinary cultures where different species were favored as either surrogates for humans or representatives of more general biological groups.

  16. Mapping the E-Government Research with Social Network Analysis

    NASA Astrophysics Data System (ADS)

    Erman, Nuša; Todorovski, Ljupčo

    About fifteen years of e-government research (EGR) lead to a research field that is looking forward to define an identity as a proper and autonomous scientific discipline. This paper proposes the use of social network analysis as a methodology for building a map of EGR and consequently contributing to the process of establishing EGR identity. The paper analyzes the network of citation between authors induced by papers published in the four proceedings of this conference (International Conference on e-Government) in the period from 2005 to 2008. The analysis helps us identify the authors that had most influence on the EGR field development and relate them to the thematic topics that prevailed the conference papers in the last four years.

  17. Research on the Simulation of Neural Networks and Semaphores

    NASA Astrophysics Data System (ADS)

    Zhu, Haibo

    In recent years, much research has been devoted to the emulation of the Turing machine; unfortunately, few have enabled the exploration of SMPs. Given the current status of decentralized algorithms, security experts obviously desire the significant unification of wide-area networks and telephony, which embodies the confusing principles of steganography. In this paper, we present new empathic communication (Bam), demonstrating that digital-to-analog converters and checksums are largely incompatible.

  18. Structure and Evolution of Scientific Collaboration Networks in a Modern Research Collaboratory

    ERIC Educational Resources Information Center

    Pepe, Alberto

    2010-01-01

    This dissertation is a study of scientific collaboration at the Center for Embedded Networked Sensing (CENS), a modern, multi-disciplinary, distributed laboratory involved in sensor network research. By use of survey research and network analysis, this dissertation examines the collaborative ecology of CENS in terms of three networks of…

  19. The Mid-South clinical Data Research Network.

    PubMed

    Rosenbloom, S Trent; Harris, Paul; Pulley, Jill; Basford, Melissa; Grant, Jason; DuBuisson, Allison; Rothman, Russell L

    2014-01-01

    The Mid-South Clinical Data Research Network (CDRN) encompasses three large health systems: (1) Vanderbilt Health System (VU) with electronic medical records for over 2 million patients, (2) the Vanderbilt Healthcare Affiliated Network (VHAN) which currently includes over 40 hospitals, hundreds of ambulatory practices, and over 3 million patients in the Mid-South, and (3) Greenway Medical Technologies, with access to 24 million patients nationally. Initial goals of the Mid-South CDRN include: (1) expansion of our VU data network to include the VHAN and Greenway systems, (2) developing data integration/interoperability across the three systems, (3) improving our current tools for extracting clinical data, (4) optimization of tools for collection of patient-reported data, and (5) expansion of clinical decision support. By 18 months, we anticipate our CDRN will robustly support projects in comparative effectiveness research, pragmatic clinical trials, and other key research areas and have the capacity to share data and health information technology tools nationally. PMID:24821742

  20. Research and services partnerships: the practice research network: a successful collaboration in Maryland.

    PubMed

    Sundeen, Sandra J; Goldman, Howard H; Nieberding, Daniel J; Piez, Deborah A; Buchanan, Robert W

    2013-05-01

    The Practice Research Network (PRN) in Maryland, funded by a grant from the National Institute of Mental Health, extends the historically close collaborative relationship between the Department of Psychiatry at the University of Maryland and the Maryland Mental Hygiene Administration. The PRN focuses on the relationship between university-based investigators and participants in the public mental health system by using local mental health authorities (Core Service Agencies) as the point of contact. PRN staff serve as liaisons to foster partnerships between university researchers and practitioners. The PRN has identified a broader range of research participants by establishing contacts with provider agencies and stakeholder groups. It has addressed concerns about research participation by meeting with consumer and family groups and arranging for investigators to present research projects to stakeholders. This approach to developing a statewide network in support of mental health research can serve as a model for other state and university partnerships.

  1. Trial geography, pharmacogenetics, and global drug development.

    PubMed

    Schuck, R N; Florian, J; Charlab, R; Pacanowski, M

    2015-03-01

    Drug development is increasingly global. The benefits of multiregional trials include worldwide evaluation of safety and efficacy. However, clinical practice, environmental, and genetic factors can vary across geographic regions, significantly influencing trial outcomes within a specific geographic region or the global population relative to the United States (US). Genomic technologies and research discoveries continue to advance at a remarkable pace, offering opportunities to explore intrinsic factors that could account for regional variability in drug pharmacokinetics or response.

  2. Pharmacogenetics and Personalized Medicine in Pain Management.

    PubMed

    Webster, Lynn R; Belfer, Inna

    2016-09-01

    Genetic research heralds a new therapeutic approach to pain management. Increasing literature demonstrates individual genetic vulnerabilities to specific pain types and mechanisms, partially explaining differing responses to similar pain stimuli. Furthermore, analgesics demonstrate great variability among carriers of different genotypes. Family history and genotyping promise to play an important role in the future approach to pain therapies. As advances continue in the genetics of pain and analgesia, pharmacotherapy will depend more on an individualized, targeted approach and less on empiricism. PMID:27514464

  3. Integration of pharmacogenetics and pharmacogenomics in drug development: implications for regulatory and medical decision making in pediatric diseases.

    PubMed

    Piana, Chiara; Surh, Linda; Furst-Recktenwald, Sabine; Iolascon, Achille; Jacqz-Aigrain, Evelyne M; Jonker, Ineke; Russo, Roberta; van Schaik, Ron H N; Wessels, Judith; Della Pasqua, Oscar E

    2012-05-01

    This article aims to provide an overview of the current situation regarding pharmacogenetic and pharmacogenomic (PG) studies in pediatrics, with a special focus on the role of PG data in the regulatory decision-making process. Despite the gap in pharmacogenetic research due to the lack of translational studies in adults and children, several technologies exist in drug development and biomarkers validation, which could supply valuable information concerning labeling and dosing recommendations. If performed under strict good clinical practice quality criteria, such findings could be included in the submission package of new chemical entities and used as additional information for prescribers, supporting further evaluation and understanding of the efficacy and safety profile of new medicines. Even though regulatory authorities may be aware of the potential role of PG in medical practice and guidances are available about the integration of PG in drug development, most data obtained from PG studies are not used by prescribers. The challenge is to better understand whether PG markers can be used to assess potential differences in drug response during the clinical program, so PG data can be integrated into the regulatory decision-making process, enabling the introduction of labeling information that promotes optimal dosing in the pediatric population. PMID:21566202

  4. The Special Populations Networks for cancer awareness research and training.

    PubMed

    Chu, Kenneth C; Jackson, Frank E

    2004-09-01

    The Special Populations Networks (SPN) project is widely regarded as perhaps the most successful in the history of the National Cancer Institute (NCI) at performing cancer awareness, research, and training activities within minority and underserved communities throughout the United States and its territories. Key to that success is the trust established among the community, its researchers and the NCI. Composed of 18 separate grant awards, the SPN project was implemented in April 2000 to integrate the communities' need for cancer information with the NCI's need to increase cancer awareness, perform new research, and train minority junior investigators for research in populations with a disproportionate burden of cancer. To date, the 18 networks have conducted more than 1,000 awareness events, trained more than 2,000 community health aides, won 135 grants to support pilot research projects, published 130 peer-reviewed papers, and raised another $20 million to support SPN activities. Successful implementation of the SPN project required the principal investigators to establish and maintain close working relationships with key community leaders and organizations in cooperation with NCI. PMID:16281704

  5. International research through networking: an old idea with new tools.

    PubMed

    Henson, J B; Rodewald, E

    1995-03-01

    The growth and refinement of electronic media capabilities, Internet, other electronic highways, fiber optics, microwaves, and satellites will have major impact on researchers and scholars, facilitating the timely sharing of information. The balance of time saved and money available may be the crucial issues in the rapidity of development. The dissemination of research results to a large audience through electronic journals, bulletin boards and data bases will become a dominant force in the formal publication of such results, with instant feedback from colleagues. The productivity of scientists and the quality of their research will be higher through better communications. Networking, however, is more than communications. It is shared interests and interaction, building on information received and provided and creating a relationship and a knowledge base to enhance international research.

  6. Enhancing research capacity of African institutions through social networking.

    PubMed

    Jimenez-Castellanos, Ana; Ramirez-Robles, Maximo; Shousha, Amany; Bagayoko, Cheick Oumar; Perrin, Caroline; Zolfo, Maria; Cuzin, Asa; Roland, Alima; Aryeetey, Richmond; Maojo, Victor

    2013-01-01

    Traditionally, participation of African researchers in top Biomedical Informatics (BMI) scientific journals and conferences has been scarce. Looking beyond these numbers, an educational goal should be to improve overall research and, therefore, to increase the number of scientists/authors able to produce and publish high quality research. In such scenario, we are carrying out various efforts to expand the capacities of various institutions located at four African countries - Egypt, Ghana, Cameroon and Mali - in the framework of a European Commission-funded project, AFRICA BUILD. This project is currently carrying out activities such as e-learning, collaborative development of informatics tools, mobility of researchers, various pilot projects, and others. Our main objective is to create a self-sustained South-South network of BMI developers.

  7. Enhancing research capacity of African institutions through social networking.

    PubMed

    Jimenez-Castellanos, Ana; Ramirez-Robles, Maximo; Shousha, Amany; Bagayoko, Cheick Oumar; Perrin, Caroline; Zolfo, Maria; Cuzin, Asa; Roland, Alima; Aryeetey, Richmond; Maojo, Victor

    2013-01-01

    Traditionally, participation of African researchers in top Biomedical Informatics (BMI) scientific journals and conferences has been scarce. Looking beyond these numbers, an educational goal should be to improve overall research and, therefore, to increase the number of scientists/authors able to produce and publish high quality research. In such scenario, we are carrying out various efforts to expand the capacities of various institutions located at four African countries - Egypt, Ghana, Cameroon and Mali - in the framework of a European Commission-funded project, AFRICA BUILD. This project is currently carrying out activities such as e-learning, collaborative development of informatics tools, mobility of researchers, various pilot projects, and others. Our main objective is to create a self-sustained South-South network of BMI developers. PMID:23920873

  8. Network of nanomedicine researches: impact of Iranian scientists

    PubMed Central

    Biglu, Mohammad-Hossein; Riazi, Shukuh

    2015-01-01

    Introduction: We may define the nanomedicine as the use of nanotechnology in the health care, disease diagnoses and treatment in order to maintain and increase the health status of a population through improve pharmacotherapy. The main objective of the current study is to analyze and visualize the co-authorship network of all papers in the field of nanomedicine published throughout 2002-2014 in journals and indexed in the Web of Science database. Methods: The Web of Science database was used to extract all papers indexed as a topic of nanomedicine through 2002-2014. The Science of Science Tool was used to map the co-authorship network of papers. Results: Total number of papers extracted from the Web of Science in the field of nanomedicine was 3092 through 2002-2014. Analysis of data showed that the research activities in the field of nanomedicine increased steadily through the period of study. USA, China, and India were the most prolific countries in the field. The dominant language of publications was English. The co-authorship connection revealed a network with a density of 0.0006. Conclusion: Nanomedicine researches have markedly been increased in Iran. Ninety-five percent of Iranian papers were cooperated with multi-authors. The collaboration coefficient degree was 0.731. PMID:26929924

  9. [Network formulaology: a new strategy for modern research of traditional Chinese medicine formulae].

    PubMed

    Fan, Xiao-Hui; Cheng, Yi-Yu; Zhang, Bo-Li

    2015-01-01

    This paper briefly analyzed and discussed the current status and major scientific challenges of traditional Chinese medicine (TCM) formulaology research. To promote formulaology research, a new strategy and corresponding technology, network formulaology, were proposed to reveal the complex interaction between functional chemome and biological responses network. The research framework and directions of network formulaology were also summarized and prospected.

  10. Network structure and the role of key players in a translational cancer research network: a study protocol

    PubMed Central

    Cunningham, Frances C; Braithwaite, Jeffrey

    2012-01-01

    Introduction Translational research networks are a deliberate strategy to bridge the gulf between biomedical research and clinical practice through interdisciplinary collaboration, supportive funding and infrastructure. The social network approach examines how the structure of the network and players who hold important positions within it constrain or enable function. This information can be used to guide network management and optimise its operations. The aim of this study was to describe the structure of a translational cancer research network (TCRN) in Australia over its first year, identify the key players within the network and explore these players' opportunities and constraints in maximising important network collaborations. Methods and analysis This study deploys a mixed-method longitudinal design using social network analysis augmented by interviews and review of TCRN documents. The study will use network documents and interviews with governing body members to explore the broader context into which the network is embedded as well as the perceptions and expectations of members. Of particular interest are the attitudes and perceptions of clinicians compared with those of researchers. A co-authorship network will be constructed of TCRN members using journal and citation databases to assess the success of past pre-network collaborations. Two whole network social network surveys will be administered 12 months apart and parameters such as density, clustering, centrality and betweenness centrality computed and compared using UCINET and Netdraw. Key players will be identified and interviewed to understand the specific activities, barriers and enablers they face in that role. Ethics and dissemination Ethics approvals were obtained from the University of New South Wales, South Eastern Sydney Northern Sector Local Health Network and Calvary Health Care Sydney. Results will be discussed with members of the TCRN, submitted to relevant journals and presented as oral

  11. European network infrastructures of observatories for terrestrial Global Change research

    NASA Astrophysics Data System (ADS)

    Vereecken, H.; Bogena, H.; Lehning, M.

    2009-04-01

    The earth's climate is significantly changing (e.g. IPCC, 2007) and thus directly affecting the terrestrial systems. The number and intensity hydrological extremes, such as floods and droughts, are continually increasing, resulting in major economical and social impacts. Furthermore, the land cover in Europe has been modified fundamentally by conversions for agriculture, forest and for other purposes such as industrialisation and urbanisation. Additionally, water resources are more than ever used for human development, especially as a key resource for agricultural and industrial activities. As a special case, the mountains of the world are of significant importance in terms of water resources supply, biodiversity, economy, agriculture, traffic and recreation but particularly vulnerable to environmental change. The Alps are unique because of the pronounced small scale variability they contain, the high population density they support and their central position in Europe. The Alps build a single coherent physical and natural environment, artificially cut by national borders. The scientific community and governmental bodies have responded to these environmental changes by performing dedicated experiments and by establishing environmental research networks to monitor, analyse and predict the impact of Global Change on different terrestrial systems of the Earths' environment. Several European network infrastructures for terrestrial Global Change research are presently immerging or upgrading, such as ICOS, ANAEE, LifeWatch or LTER-Europe. However, the strongest existing networks are still operating on a regional or national level and the historical growth of such networks resulted in a very heterogeneous landscape of observation networks. We propose therefore the establishment of two complementary networks: The NetwOrk of Hydrological observAtories, NOHA. NOHA aims to promote the sustainable management of water resources in Europe, to support the prediction of

  12. Study of co-authorship network of papers in the Journal of Research in Medical Sciences using social network analysis

    PubMed Central

    Zare-Farashbandi, Firoozeh; Geraei, Ehsan; Siamaki, Saba

    2014-01-01

    Background: Co-authorship is one of the most tangible forms of research collaboration. A co-authorship network is a social network in which the authors through participation in one or more publication through an indirect path have linked to each other. The present research using the social network analysis studied co-authorship network of 681 articles published in Journal of Research in Medical Sciences (JRMS) during 2008-2012. Materials and Methods: The study was carried out with the scientometrics approach and using co-authorship network analysis of authors. The topology of the co-authorship network of 681 published articles in JRMS between 2008 and 2012 was analyzed using macro-level metrics indicators of network analysis such as density, clustering coefficient, components and mean distance. In addition, in order to evaluate the performance of each authors and countries in the network, the micro-level indicators such as degree centrality, closeness centrality and betweenness centrality as well as productivity index were used. The UCINET and NetDraw softwares were used to draw and analyze the co-authorship network of the papers. Results: The assessment of the authors productivity in this journal showed that the first ranks were belonged to only five authors, respectively. Furthermore, analysis of the co-authorship of the authors in the network demonstrated that in the betweenness centrality index, three authors of them had the good position in the network. They can be considered as the network leaders able to control the flow of information in the network compared with the other members based on the shortest paths. On the other hand, the key role of the network according to the productivity and centrality indexes was belonged to Iran, Malaysia and United States of America. Conclusion: Co-authorship network of JRMS has the characteristics of a small world network. In addition, the theory of 6° separation is valid in this network was also true. PMID:24672564

  13. The AERONET network: atmospheric aerosol research in Ukraine

    NASA Astrophysics Data System (ADS)

    Milinevsky, G. P.

    2013-12-01

    The AERONET network is one of the most developed ground-based networks for aerosol monitoring. Solar radiance extinction, aureole brightness and sky light polarization measurements are used by the AERONET inversion retrieval algorithm to derive a variety of aerosol particle properties and parameters that are important for estimations of aerosol influences on air quality and climate change. In 2008 the AERONET has been extended in Ukraine: in addition to Sevastopol site (operated since 2006) the sunphotometer CIMEL CE318-2 has been installed at Kyiv site. New generation of sunphotometer (CE318N) has been used widely since 2011 in various sites of Ukraine as mobile station together with portable sunphotometer Microtops II. This article presents a short description of the AERONET, its development in Ukraine and prospects for future atmospheric research.

  14. The Utrecht Pharmacy Practice network for Education and Research: a network of community and hospital pharmacies in the Netherlands.

    PubMed

    Koster, Ellen S; Blom, Lyda; Philbert, Daphne; Rump, Willem; Bouvy, Marcel L

    2014-08-01

    Practice-based networks can serve as effective mechanisms for the development of the profession of pharmacists, on the one hand by supporting student internships and on the other hand by collection of research data and implementation of research outcomes among public health practice settings. This paper presents the characteristics and benefits of the Utrecht Pharmacy Practice network for Education and Research, a practice based research network affiliated with the Department of Pharmaceutical Sciences of Utrecht University. Yearly, this network is used to realize approximately 600 student internships (in hospital and community pharmacies) and 20 research projects. To date, most research has been performed in community pharmacy and research questions frequently concerned prescribing behavior or adherence and subjects related to uptake of regulations in the pharmacy setting. Researchers gain access to different types of data from daily practice, pharmacists receive feedback on the functioning of their own pharmacy and students get in depth insight into pharmacy practice.

  15. Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions.

    PubMed

    Madadi, Parvaz; Hildebrandt, Doris; Gong, Inna Y; Schwarz, Ute I; Ciszkowski, Catherine; Ross, Colin J D; Sistonen, Johanna; Carleton, Bruce C; Hayden, Michael R; Lauwers, Albert E; Koren, Gideon

    2010-10-01

    Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.

  16. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    PubMed Central

    Babalola, Chinedum Peace; Morse, Gene D.; Taiwo, Babafemi

    2016-01-01

    Neurological complications associated with the human immunodeficiency virus (HIV) are a matter of great concern. While antiretroviral (ARV) drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity. PMID:27777797

  17. Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.

    PubMed

    Brown, Jacob T; Bishop, Jeffrey R

    2015-01-01

    Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder and is predominantly metabolized by the CYP2D6 enzyme. Differences in pharmacokinetic parameters as well as clinical treatment outcomes across CYP2D6 genotype groups have resulted in dosing recommendations within the product label, but clinical studies supporting the use of genotype guided dosing are currently lacking. Furthermore, pharmacokinetic and clinical studies have primarily focused on extensive as compared with poor metabolizers, with little information known about other metabolizer categories as well as genes involved in the pharmacodynamics of atomoxetine. This review describes the pharmacogenetic associations with atomoxetine pharmacokinetics, treatment response and tolerability with considerations for the clinical utility of this information.

  18. Update on thiopurine pharmacogenetics in inflammatory bowel disease.

    PubMed

    Roberts, Rebecca L; Barclay, Murray L

    2015-07-01

    Azathioprine and 6-mercaptopurine remain pivotal therapies for the maintenance of disease remission in patients with Crohn's disease and ulcerative colitis. While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance. In recent years, a number of other genetic polymorphisms have received increasing attention in the literature. In particular, SNPs in NUDT15 and in the class II HLA locus have been shown to predict thiopurine-related leukopenia and pancreatitis. The aim of this review is to provide a concise update of genetic variability which may influence patient response to azathioprine and 6-mercaptopurine.

  19. Pharmacogenetics of topical and systemic treatment of psoriasis.

    PubMed

    Prieto-Pérez, Rocío; Cabaleiro, Teresa; Daudén, Esteban; Ochoa, Dolores; Román, Manuel; Abad-Santos, Francisco

    2013-10-01

    Psoriasis is a chronic inflammatory skin disease. The cause of psoriasis is unknown, although genetics may play a key role in its development. Treatment of the disease varies with severity. Topical drugs, such as corticosteroids, coal tar, retinoids and vitamin D analogs, are commonly used to treat mild psoriasis. Phototherapy and systemic drugs, such as calcineurin inhibitors, methotrexate, acitretin and biological drugs, are usually used to treat moderate-to-severe psoriasis. Not all patients respond well to treatment, and some can develop severe adverse effects. Interindividual differences in several genes may explain this variation in response to treatment. Pharmacogenetics and pharmacogenomics can facilitate more personalized medicine and prevent the adverse effects associated with treatment.

  20. Relevance of G-quadruplex structures to pharmacogenetics.

    PubMed

    Cree, Simone L; Kennedy, Martin A

    2014-01-01

    G-quadruplexes are non-canonical secondary structures formed within nucleic acids that are involved in modulating cellular processes such as replication, gene regulation, recombination and epigenetics. Within genes, there is mounting evidence of G-quadruplex involvement in transcriptional and post transcriptional regulation. We report the presence of potential G-quadruplex motifs within relevant sites of some important pharmacogenes and discuss the possible implications of this on the function and expression of these genes. Appreciating the location and potential functions of these motifs may be of value when considering the impacts of some pharmacogenetic variants. G-quadruplexes are also the focus of drug development efforts in oncology and we highlight the broader pharmacological implications of treatment strategies that may target G-quadruplexes.

  1. Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy.

    PubMed

    Weng, Liming; Zhang, Li; Peng, Yan; Huang, R Stephanie

    2013-02-01

    In the past decade, advances in pharmacogenetics and pharmacogenomics (PGx) have gradually unveiled the genetic basis of interindividual differences in drug responses. A large portion of these advances have been made in the field of anticancer therapy. Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information. Given the complexity of this genetic information (e.g., tumor mutation and gene overexpression, chromosomal translocation and germline variations), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs. In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects. Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets.

  2. Precision Obesity Treatments Including Pharmacogenetic and Nutrigenetic Approaches.

    PubMed

    Solas, Maite; Milagro, Fermin I; Martínez-Urbistondo, Diego; Ramirez, Maria J; Martínez, J Alfredo

    2016-07-01

    Five pharmaceutical strategies are currently approved by the US FDA for the treatment of obesity: orlistat, lorcaserin, liraglutide, phentermine/topiramate, and bupropion/naltrexone. The most effective treatment seems to be the combined administration of phentermine/topiramate followed by lorcaserin and bupropion/naltrexone. In relation to the management of excessive weight, other aspects also need to be considered, including comorbidities accompanying obesity, drug interactions, and the risk of negative collateral effects, as well as individualized treatments based on the genetic make-up. This review aims to provide an overview of the approved anti-obesity drugs and newer molecules that could affect different targets in the central nervous system or peripheral tissues, the molecular mechanisms, emerging dietary treatments and phytogenic compounds, and pharmacogenetic/nutrigenetic approaches for personalized obesity management. PMID:27236593

  3. Knowledge brokers in a knowledge network: the case of Seniors Health Research Transfer Network knowledge brokers

    PubMed Central

    2013-01-01

    Background The purpose of this paper is to describe and reflect on the role of knowledge brokers (KBs) in the Seniors Health Research Transfer Network (SHRTN). The paper reviews the relevant literature on knowledge brokering, and then describes the evolving role of knowledge brokering in this knowledge network. Methods The description of knowledge brokering provided here is based on a developmental evaluation program and on the experiences of the authors. Data were gathered through qualitative and quantitative methods, analyzed by the evaluators, and interpreted by network members who participated in sensemaking forums. The results were fed back to the network each year in the form of formal written reports that were widely distributed to network members, as well as through presentations to the network’s members. Results The SHRTN evaluation and our experiences as evaluators and KBs suggest that a SHRTN KB facilitates processes of learning whereby people are connected with tacit or explicit knowledge sources that will help them to resolve work-related challenges. To make this happen, KBs engage in a set of relational, technical, and analytical activities that help communities of practice (CoPs) to develop and operate, facilitate exchanges among people with similar concerns and interests, and help groups and individuals to create, explore, and apply knowledge in their practice. We also suggest that the role is difficult to define, emergent, abstract, episodic, and not fully understood. Conclusions The KB role within this knowledge network has developed and matured over time. The KB adapts to the social and technical affordances of each situation, and fashions a unique and relevant process to create relationships and promote learning and change. The ability to work with teams and to develop relevant models and feasible approaches are critical KB skills. The KB is a leader who wields influence rather than power, and who is prepared to adopt whatever roles and

  4. Finding Collaborators: Toward Interactive Discovery Tools for Research Network Systems

    PubMed Central

    Schleyer, Titus K; Becich, Michael J; Hochheiser, Harry

    2014-01-01

    Background Research networking systems hold great promise for helping biomedical scientists identify collaborators with the expertise needed to build interdisciplinary teams. Although efforts to date have focused primarily on collecting and aggregating information, less attention has been paid to the design of end-user tools for using these collections to identify collaborators. To be effective, collaborator search tools must provide researchers with easy access to information relevant to their collaboration needs. Objective The aim was to study user requirements and preferences for research networking system collaborator search tools and to design and evaluate a functional prototype. Methods Paper prototypes exploring possible interface designs were presented to 18 participants in semistructured interviews aimed at eliciting collaborator search needs. Interview data were coded and analyzed to identify recurrent themes and related software requirements. Analysis results and elements from paper prototypes were used to design a Web-based prototype using the D3 JavaScript library and VIVO data. Preliminary usability studies asked 20 participants to use the tool and to provide feedback through semistructured interviews and completion of the System Usability Scale (SUS). Results Initial interviews identified consensus regarding several novel requirements for collaborator search tools, including chronological display of publication and research funding information, the need for conjunctive keyword searches, and tools for tracking candidate collaborators. Participant responses were positive (SUS score: mean 76.4%, SD 13.9). Opportunities for improving the interface design were identified. Conclusions Interactive, timeline-based displays that support comparison of researcher productivity in funding and publication have the potential to effectively support searching for collaborators. Further refinement and longitudinal studies may be needed to better understand the

  5. Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics).

    PubMed

    Ozdemir, Vural; Endrenyi, Laszlo; Aynacıoğlu, Sükrü; Bragazzi, Nicola Luigi; Dandara, Collet; Dove, Edward S; Ferguson, Lynnette R; Geraci, Christy Jo; Hafen, Ernst; Kesim, Belgin Eroğlu; Kolker, Eugene; Lee, Edmund J D; Llerena, Adrian; Nacak, Muradiye; Shimoda, Kazutaka; Someya, Toshiyuki; Srivastava, Sanjeeva; Tomlinson, Brian; Vayena, Effy; Warnich, Louise; Yaşar, Umit

    2014-04-01

    This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way

  6. Earth Stewardship Science: International Research Networks based in Africa (Invited)

    NASA Astrophysics Data System (ADS)

    Gaines, S. M.

    2010-12-01

    The role of networking in student and early career years is critical in the development of international interdisciplinary earth system science. These networks - both peer and mentor-based - can build community, foster enthusiasm and further research applications in addition to the traditional goal of identifying and obtaining work. UNESCO has nearly 40 years of experience in building international research teams through the International Geoscience Program (IGCP) and has recently focused their attention on the status of the earth sciences in Africa. UNESCO’s Earth Science Education Initiative in Africa ran a series of regional scoping workshops around the continent in order to develop an integrated status report on the earth sciences in Africa. The results, which are globally relevant, indicate that the field is limited by the level of basic science education of incoming students and restricted laboratory facilities, but also by a lack of connectedness. This isolation relates both to the interaction between researchers within countries and around the world but also the divide between Universities and Industry and the failure of the field to communicate its relevance to the public. In a context where livelihood opportunities are the driver of study and the earth sciences provide a major source of income, practical academic ties to industry are an essential element of the attractiveness of the field to students. Actions and ideas for addressing this situation will be presented to reinforce the role of the earth sciences in improving human and environmental well-being.

  7. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    PubMed Central

    2016-01-01

    With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA) based on gene coexpression network (GCN) increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  8. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    PubMed Central

    2016-01-01

    With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA) based on gene coexpression network (GCN) increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies. PMID:27597964

  9. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research.

    PubMed

    Li, Junyi; Li, Yi-Xue; Li, Yuan-Yuan

    2016-01-01

    With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA) based on gene coexpression network (GCN) increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies. PMID:27597964

  10. Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies.

    PubMed

    Bonvicini, C; Faraone, S V; Scassellati, C

    2016-07-01

    found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD. PMID:27217152

  11. Transforming networking within the ESIP Federation using ResearchBit

    NASA Astrophysics Data System (ADS)

    Robinson, E.

    2015-12-01

    Geoscientists increasingly need interdisciplinary teams to solve their research problems. Currently, geoscientists use Research Networking (RN) systems to connect with each other and find people of similar and dissimilar interests. As we shift to digitally mediated scholarship, we need innovative methods for scholarly communication. Formal methods for scholarly communication are undergoing vast transformation owing to the open-access movement and reproducible research. However, informal scholarly communication that takes place at professional society meetings and conferences, like AGU, has received limited research attention relying primarily on serendipitous interaction. The ResearchBit project aims to fundamentally improve informal methods of scholarly communication by leveraging the serendipitous interactions of researchers and making them more aware of co-located potential collaborators with mutual interests. This presentation will describe our preliminary hardware testing done at the Federation for Earth Science Information Partners (ESIP) Summer meeting this past July and the initial recommendation system design. The presentation will also cover the cultural shifts and hurdles to introducing new technology, the privacy concerns of tracking technology and how we are addressing those new issues.

  12. The role of social networking sites in medical genetics research.

    PubMed

    Reaves, Allison Cook; Bianchi, Diana W

    2013-05-01

    Social networking sites (SNS) have potential value in the field of medical genetics as a means of research subject recruitment and source of data. This article examines the current role of SNS in medical genetics research and potential applications for these sites in future studies. Facebook is the primary SNS considered, given the prevalence of its use in the United States and role in a small but growing number of studies. To date, utilization of SNS in medical genetics research has been primarily limited to three studies that recruited subjects from populations of Facebook users [McGuire et al. (2009); Am J Bioeth 9: 3-10; Janvier et al. (2012); Pediatrics 130: 293-298; Leighton et al. (2012); Public Health Genomics 15: 11-21]. These studies and a number of other medical and public health studies that have used Facebook as a context for recruiting research subjects are discussed. Approaches for Facebook-based subject recruitment are identified, including paid Facebook advertising, snowball sampling, targeted searching and posting. The use of these methods in medical genetics research has the potential to facilitate cost-effective research on both large, heterogeneous populations and small, hard-to-access sub-populations. PMID:23554131

  13. Extremely high data-rate, reliable network systems research

    NASA Technical Reports Server (NTRS)

    Foudriat, E. C.; Maly, Kurt J.; Mukkamala, R.; Murray, Nicholas D.; Overstreet, C. Michael

    1990-01-01

    Significant progress was made over the year in the four focus areas of this research group: gigabit protocols, extensions of metropolitan protocols, parallel protocols, and distributed simulations. Two activities, a network management tool and the Carrier Sensed Multiple Access Collision Detection (CSMA/CD) protocol, have developed to the point that a patent is being applied for in the next year; a tool set for distributed simulation using the language SIMSCRIPT also has commercial potential and is to be further refined. The year's results for each of these areas are summarized and next year's activities are described.

  14. Ethical reflections on pharmacogenetics and DNA banking in a cohort of HIV-infected patients

    PubMed Central

    de Montgolfier, Sandrine; Moutel, Grégoire; Duchange, Nathalie; Theodorou, Ioannis; Hervé, Christian; Leport, Catherine

    2002-01-01

    The aim of this study was to analyze ethical questions concerning the storage of human biological samples to be used in genetic analyses and pharmacogenetic research based on a French experience of DNA banking in a cohort of HIV-infected patients receiving protease inhibitor treatment (APROCO). We describe the ethical issues raised during the establishment of a DNA bank, including questions dealing with autonomy, benefit to the patient, information sharing and confidentiality as well as guarantees concerning the storage and use of DNA. We describe the practical applications of themes illustrated theoretically in the literature. Most of the points raised are not specific to HIV, but some of them may be more accurate due to the characteristics of the HIV population. The questions raised are not exhaustive and we conclude with specific points that remain to be defined. Our results are summarized in the memorandum and consent form presented in the appendices. This work should allow other researchers and members of evaluation committees to enrich their considerations and should stimulate discussion on this subject. PMID:12464796

  15. Ethical reflections on pharmacogenetics and DNA banking in a cohort of HIV-infected patients.

    PubMed

    de Montgolfier, Sandrine; Moutel, Grégoire; Duchange, Nathalie; Theodorou, Ioannis; Hervé, Christian; Leport, Catherine

    2002-12-01

    The aim of this study was to analyse ethical issues concerning the storage of human biological samples to be used in genetic analyses and pharmacogenetic research based on a French experience of DNA banking in a cohort of human immunodeficiency virus (HIV)-infected patients started on a protease inhibitor-containing treatment. We describe the ethical issues raised during the establishment of a DNA bank, including questions dealing with autonomy, benefit to the patient, information sharing and confidentiality as well as guarantees concerning the storage and use of DNA. The practical applications of themes illustrated theoretically in the literature are discussed. Most of the points raised are not specific to HIV, but some of them may be more accurate due to the characteristics of the HIV population, which is more involved in the social debate through the community life and the increased risk of stigmatization. Our results are summarized in the memorandum and consent form presented in the Appendices. One issue still open to discussion is the way the results of genetic data will be given to the patients. This work should allow other researchers and members of evaluation committees to enrich their considerations and should stimulate discussion on this topic.

  16. The promise of pharmacogenetics: assessing the prospects for disease and patient stratification.

    PubMed

    Smart, Andrew; Martin, Paul

    2006-09-01

    Pharmacogenetics is an emerging biotechnology concerned with understanding the genetic basis of drug response, and promises to transform the development, marketing and prescription of medicines. This paper is concerned with analysing the move towards segmented drug markets, which is implicit in the commercial development of pharmacogenetics. It is claimed that in future who gets a particular drug will be determined by their genetic make up. Drawing on ideas from the sociology of expectations we examine how pharmaceutical and biotechnology companies are constructing, responding to and realising particular 'visions' or expectations of pharmacogenetics and market stratification. We argue that the process of market segmentation remains uncertain, but that the outcome will be fashioned according to the convergence and divergence of the interests of key commercial actors. Qualitative data based both on interviews with industry executives and company documentation will be used to explore how different groups of companies are developing pharmacogenetics in distinct ways, and what consequences these different pathways might have for both clinical practice and health policy. In particular, the analysis will show a convergence of interests between biotechnology and pharmaceutical companies for creating segmented markets for new drugs, but a divergence of interest in segmenting established markets. Whilst biotechnology firms have a strong incentive to innovate, the pharmaceutical industry has no commercial interest in segmenting markets for existing products. This has important implications, as many of the claimed public health benefits of pharmacogenetics will derive from changing the prescribing of existing medicines. One significant implication of this is that biotechnology companies who wish to apply pharmacogenetics to existing medicines will have to explore an alternative convergence of interests with healthcare payers and providers (health insurers, HMOs, MCOs and

  17. The MAPP research network: design, patient characterization and operations

    PubMed Central

    2014-01-01

    Background The “Multidisciplinary Approach to the Study of Chronic Pelvic Pain” (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network’s central study and common data elements are described. Methods The primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as “positive” controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended

  18. Research and collaboration overview of Institut Pasteur International Network: a bibliometric approach toward research funding decisions

    PubMed Central

    Mostafavi, Ehsan; Bazrafshan, Azam

    2014-01-01

    Background: Institut Pasteur International Network (IPIN), which includes 32 research institutes around the world, is a network of research and expertise to fight against infectious diseases. A scientometric approach was applied to describe research and collaboration activities of IPIN. Methods: Publications were identified using a manual search of IPIN member addresses in Science Citation Index Expanded (SCIE) between 2006 and 2011. Total publications were then subcategorized by geographic regions. Several scientometric indicators and the H-index were employed to estimate the scientific production of each IPIN member. Subject and geographical overlay maps were also applied to visualize the network activities of the IPIN members. Results: A total number of 12667 publications originated from IPIN members. Each author produced an average number of 2.18 papers and each publication received an average of 13.40 citations. European Pasteur Institutes had the largest amount of publications, authored papers, and H-index values. Biochemistry and molecular biology, microbiology, immunology and infectious diseases were the most important research topics, respectively. Geographic mapping of IPIN publications showed wide international collaboration among IPIN members around the world. Conclusion: IPIN has strong ties with national and international authorities and organizations to investigate the current and future health issues. It is recommended to use scientometric and collaboration indicators as measures of research performance in IPIN future policies and investment decisions. PMID:24596896

  19. Networking among young global health researchers through an intensive training approach: a mixed methods exploratory study

    PubMed Central

    2014-01-01

    Background Networks are increasingly regarded as essential in health research aimed at influencing practice and policies. Less research has focused on the role networking can play in researchers’ careers and its broader impacts on capacity strengthening in health research. We used the Canadian Coalition for Global Health Research (CCGHR) annual Summer Institute for New Global Health Researchers (SIs) as an opportunity to explore networking among new global health researchers. Methods A mixed-methods exploratory study was conducted among SI alumni and facilitators who had participated in at least one SI between 2004 and 2010. Alumni and facilitators completed an online short questionnaire, and a subset participated in an in-depth interview. Thematic analysis of the qualitative data was triangulated with quantitative results and CCGHR reports on SIs. Synthesis occurred through the development of a process model relevant to networking through the SIs. Results Through networking at the SIs, participants experienced decreased isolation and strengthened working relationships. Participants accessed new knowledge, opportunities, and resources through networking during the SI. Post-SI, participants reported ongoing contact and collaboration, although most participants desired more opportunities for interaction. They made suggestions for structural supports to networking among new global health researchers. Conclusions Networking at the SI contributed positively to opportunities for individuals, and contributed to the formation of a network of global health researchers. Intentional inclusion of networking in health research capacity strengthening initiatives, with supportive resources and infrastructure could create dynamic, sustainable networks accessible to global health researchers around the world. PMID:24460819

  20. Exploration of heterogeneity in distributed research network drug safety analyses.

    PubMed

    Hansen, Richard A; Zeng, Peng; Ryan, Patrick; Gao, Juan; Sonawane, Kalyani; Teeter, Benjamin; Westrich, Kimberly; Dubois, Robert W

    2014-12-01

    Distributed data networks representing large diverse populations are an expanding focus of drug safety research. However, interpreting results is difficult when treatment effect estimates vary across datasets (i.e., heterogeneity). In a previous study, risk estimates were generated for selected drugs and potential adverse outcomes. Analyses were replicated across eight distributed data sources using an identical analytic structure. To evaluate heterogeneity of risk estimates across data sources, the estimates were combined with summary-level data characterizing the population of each data source. Meta-analysis, meta-regression, and plots of the influence on overall results versus contribution to heterogeneity were examined and used to illustrate an approach to heterogeneity assessment. Heterogeneity, as measured by the I-squared statistic, was high with variability across outcomes. Plots of the relationship between influence on overall results and contribution to heterogeneity suggest that certain datasets and characteristics were influential but there was variability dependent on the drug and outcome being assessed. Exploratory meta-regression identified many possible influential factors, but may be subject to ecological bias and false positive conclusions. Distributed data network drug safety analyses can produce heterogeneous risk estimates that may not be easily explained. Approaches illustrated here can be useful for research that is subject to similar problems with heterogeneity. PMID:26052957

  1. Exploration of heterogeneity in distributed research network drug safety analyses.

    PubMed

    Hansen, Richard A; Zeng, Peng; Ryan, Patrick; Gao, Juan; Sonawane, Kalyani; Teeter, Benjamin; Westrich, Kimberly; Dubois, Robert W

    2014-12-01

    Distributed data networks representing large diverse populations are an expanding focus of drug safety research. However, interpreting results is difficult when treatment effect estimates vary across datasets (i.e., heterogeneity). In a previous study, risk estimates were generated for selected drugs and potential adverse outcomes. Analyses were replicated across eight distributed data sources using an identical analytic structure. To evaluate heterogeneity of risk estimates across data sources, the estimates were combined with summary-level data characterizing the population of each data source. Meta-analysis, meta-regression, and plots of the influence on overall results versus contribution to heterogeneity were examined and used to illustrate an approach to heterogeneity assessment. Heterogeneity, as measured by the I-squared statistic, was high with variability across outcomes. Plots of the relationship between influence on overall results and contribution to heterogeneity suggest that certain datasets and characteristics were influential but there was variability dependent on the drug and outcome being assessed. Exploratory meta-regression identified many possible influential factors, but may be subject to ecological bias and false positive conclusions. Distributed data network drug safety analyses can produce heterogeneous risk estimates that may not be easily explained. Approaches illustrated here can be useful for research that is subject to similar problems with heterogeneity.

  2. The Global Research Collaboration of Network Meta-Analysis: A Social Network Analysis

    PubMed Central

    Li, Lun; Catalá-López, Ferrán; Alonso-Arroyo, Adolfo; Tian, Jinhui; Aleixandre-Benavent, Rafael; Pieper, Dawid; Ge, Long; Yao, Liang; Wang, Quan; Yang, Kehu

    2016-01-01

    Background and Objective Research collaborations in biomedical research have evolved over time. No studies have addressed research collaboration in network meta-analysis (NMA). In this study, we used social network analysis methods to characterize global collaboration patterns of published NMAs over the past decades. Methods PubMed, EMBASE, Web of Science and the Cochrane Library were searched (at 9th July, 2015) to include systematic reviews incorporating NMA. Two reviewers independently selected studies and cross-checked the standardized data. Data was analyzed using Ucinet 6.0 and SPSS 17.0. NetDraw software was used to draw social networks. Results 771 NMAs published in 336 journals from 3459 authors and 1258 institutions in 49 countries through the period 1997–2015 were included. More than three-quarters (n = 625; 81.06%) of the NMAs were published in the last 5-years. The BMJ (4.93%), Current Medical Research and Opinion (4.67%) and PLOS One (4.02%) were the journals that published the greatest number of NMAs. The UK and the USA (followed by Canada, China, the Netherlands, Italy and Germany) headed the absolute global productivity ranking in number of NMAs. The top 20 authors and institutions with the highest publication rates were identified. Overall, 43 clusters of authors (four major groups: one with 37 members, one with 12 members, one with 11 members and one with 10 members) and 21 clusters of institutions (two major groups: one with 62 members and one with 20 members) were identified. The most prolific authors were affiliated with academic institutions and private consulting firms. 181 consulting firms and pharmaceutical industries (14.39% of institutions) were involved in 199 NMAs (25.81% of total publications). Although there were increases in international and inter-institution collaborations, the research collaboration by authors, institutions and countries were still weak and most collaboration groups were small sizes. Conclusion Scientific

  3. Developing a clinical research network: the Northern Region Endoscopy Group experience.

    PubMed

    Rajasekhar, Praveen; Rees, Colin; Rutter, Matthew; Hungin, Pali

    2014-04-01

    Research is central to the National Health Service. Clinical trial recruitment has been aided by the National Institute for Health Research's Comprehensive Research Network but these networks do not support development of research. The Northern Region Endoscopy Group (NREG) was founded in 2007, encompasses 17 endoscopy units and has become a highly successful collaborative research network. The network is now a major contributor to UK trials, has published over 20 papers (>60 abstracts) and holds grants totalling more than £1.5 million. The NREG provides an exemplar model of how collaborative working can contribute significantly to biomedical research.

  4. Primary Care Practice-Based Research Networks: Working at the Interface Between Research and Quality Improvement

    PubMed Central

    Mold, James W.; Peterson, Kevin A.

    2005-01-01

    PURPOSE We wanted to describe the emerging role of primary care practice-based in research, quality improvement (QI), and translation of research into practice (TRIP). METHODS We gathered information from the published literature, discussions with PBRN leaders, case examples, and our own personal experience to describe a role for PBRNs that comfortably bridges the gap between research and QI, discovery and application, academicians and practitioners—a role that may lead to the establishment of true learning communities. We provide specific recommendations for network directors, network clinicians, and other potential stakeholders. RESULTS PBRNs function at the interface between research and QI, an interface called TRIP by some members of the research community. In doing so, PBRNs are helping to clarify the difficulty of applying study findings to everyday care as an inappropriate disconnect between discovery and implementation, research and practice. Participatory models are emerging in which stakeholders agree on their goals; apply their collective knowledge, skills, and resources to accomplish these goals; and use research and QI methods when appropriate. CONCLUSIONS PBRNs appear to be evolving from clinical laboratories into learning communities, proving grounds for generalizable solutions to clinical problems, and engines for improvement of primary care delivery systems. PMID:15928213

  5. Friending Adolescents on Social Networking Websites: A Feasible Research Tool

    PubMed Central

    Brockman, Libby N.; Christakis, Dimitri A.; Moreno, Megan A.

    2014-01-01

    Objective Social networking sites (SNSs) are increasingly used for research. This paper reports on two studies examining the feasibility of friending adolescents on SNSs for research purposes. Methods Study 1 took place on www.MySpace.com where public profiles belonging to 18-year-old adolescents received a friend request from an unknown physician. Study 2 took place on www.Facebook.com where college freshmen from two US universities, enrolled in an ongoing research study, received a friend request from a known researcher’s profile. Acceptance and retention rates of friend requests were calculated for both studies. Results Study 1: 127 participants received a friend request; participants were 18 years-old, 62.2% male and 51.8% Caucasian. 49.6% accepted the friend request. After 9 months, 76% maintained the online friendship, 12.7% defriended the study profile and 11% deactivated their profile. Study 2: 338 participants received a friend request; participants were 18 years-old, 56.5% female and 75.1% Caucasian. 99.7% accepted the friend request. Over 12 months, 3.3% defriended the study profile and 4.1% deactivated their profile. These actions were often temporary; the overall 12-month friendship retention rate was 96.1%. Conclusion Friending adolescents on SNSs is feasible and friending adolescents from a familiar profile may be more effective for maintaining online friendship with research participants over time. PMID:25485226

  6. A Penalized Likelihood Approach for Investigating Gene-Drug Interactions in Pharmacogenetic Studies

    PubMed Central

    Neely, Megan L.; Bondell, Howard D.; Tzeng, Jung-Ying

    2015-01-01

    Summary Pharmacogenetics investigates the relationship between heritable genetic variation and the variation in how individuals respond to drug therapies. Often, gene-drug interactions play a primary role in this response, and identifying these effects can aid in the development of individualized treatment regimes. Haplotypes can hold key information in understanding the association between genetic variation and drug response. However, the standard approach for haplotype-based association analysis does not directly address the research questions dictated by individualized medicine. A complementary post-hoc analysis is required, and this post-hoc analysis is usually under powered after adjusting for multiple comparisons and may lead to seemingly contradictory conclusions. In this work, we propose a penalized likelihood approach that is able to overcome the drawbacks of the standard approach and yield the desired personalized output. We demonstrate the utility of our method by applying it to the Scottish Randomized Trial in Ovarian Cancer. We also conducted simulation studies and showed that the proposed penalized method has comparable or more power than the standard approach and maintains low Type I error rates for both binary and quantitative drug responses. The largest performance gains are seen when the haplotype frequency is low, the difference in effect sizes are small, or the true relationship among the drugs is more complex. PMID:25604216

  7. Dictyostelium discoideum to human cells: pharmacogenetic studies demonstrate a role for sphingolipids in chemoresistance.

    PubMed

    Alexander, Stephen; Min, Junxia; Alexander, Hannah

    2006-03-01

    Resistance to chemotherapy is a major obstacle for the treatment of cancer and a subject of extensive research. Numerous mechanisms of drug resistance have been proposed, and they differ for different drugs. Nevertheless, it is clear that our understanding of this important problem is still incomplete, and that new targets for modulating therapy still await discovery. The attractive biology and the availability of powerful molecular techniques have made the cellular slime mold Dictyostelium discoideum, a powerful non-mammalian model for drug target discovery, and the problem of drug resistance. To understand the molecular basis of chemoresistance to the widely used drug cisplatin, both genetic and pharmacological approaches have been applied to this versatile experimental system. These studies have resulted in the identification of novel molecular pathways which can be used to increase the efficacy of cisplatin, and brought attention to the role of sphingolipids in mediating the cellular response to chemotherapeutic drugs. In the following review, we will describe the history and utility of D. discoideum in pharmacogenetics, and discuss recent studies which focus attention on the role of sphingolipids in chemotherapy and chemoresistance. PMID:16403600

  8. WEGENER: World Earthquake GEodesy Network for Environmental Hazard Research

    NASA Astrophysics Data System (ADS)

    Ozener, Haluk; Zerbini, Susanna; Bastos, Luisa; Becker, Matthias; Meghraoui, Mustapha; Reilinger, Robert

    2013-04-01

    WEGENER is originally the acronym for Working Group of European Geoscientists for the Establishment of Networks for Earth-science Research. It was founded in March 1981 in response to an appeal delivered at the Journées Luxembourgeoises de Geodynamique in December 1980 to respond with a coordinated European proposal to a NASA Announcement of Opportunity inviting participation in the Crustal Dynamics and Earthquake Research Program. WEGENER, during the past 32 years, has always kept a close contact with the Agencies and Institutions responsible for the development and maintenance of the global space geodetic networks with the aim to make them aware of the scientific needs and outcomes of the project which might have an influence on the general science policy trends. WEGENER was serving as Inter-commission Project 3.2, between Commission 1 and Commission 3, of the International Association of Geodesy (IAG) until 2012. Since then, WEGENER project has became the Sub-commission 3.5 of IAG commission 3, namely Tectonics and Earthquake Geodesy. In this study, we briefly review the accomplishments of WEGENER as originally conceived and outline and justify the new focus of the WEGENER consortium. The remarkable and rapid evolution of the present state of global geodetic monitoring in regard to the precision of positioning capabilities (and hence deformation) and global coverage, the development of InSAR for monitoring strain with unprecedented spatial resolution, and continuing and planned data from highly precise satellite gravity and altimetry missions, encourage us to shift principal attention from mainly monitoring capabilities by a combination of space and terrestrial geodetic techniques to applying existing observational methodologies to the critical geophysical phenomena that threaten our planet and society. Our new focus includes developing an improved physical basis to mitigate earthquake, tsunami, and volcanic risks, and the effects of natural and anthropogenic

  9. A Space Operations Network Alternative: Using the Globally Connected Research and Education Networks for Space-based Science Operations

    NASA Technical Reports Server (NTRS)

    Bradford, Robert N.

    2006-01-01

    Earth based networking in support of various space agency projects has been based on leased service/circuits which has a high associated cost. This cost is almost always taken from the science side resulting in less science. This is a proposal to use Research and Education Networks (RENs) worldwide to support space flight operations in general and space-based science operations in particular. The RENs were developed to support scientific and educational endeavors. They do not provide support for general Internet traffic. The connectivity and performance of the research and education networks is superb. The connectivity at Layer 3 (IP) virtually encompasses the globe. Most third world countries and all developed countries have their own research and education networks, which are connected globally. Performance of the RENs especially in the developed countries is exceptional. Bandwidth capacity currently exists and future expansion promises that this capacity will continue. REN performance statistics has always exceeded minimum requirements for spaceflight support. Research and Education networks are more loosely managed than a corporate network but are highly managed when compared to the commodity Internet. Management of RENs on an international level is accomplished by the International Network Operations Center at Indiana University at Indianapolis. With few exceptions, each regional and national REN has its own network ops center. The acceptable use policies (AUP), although differing by country, allows any scientific program or project the use of their networks. Once in compliance with the first RENs AUP, all others will accept that specific traffic including regional and transoceanic networks. RENs can support spaceflight related scientific programs and projects. Getting the science to the researcher is obviously key to any scientific project. RENs provide a pathway to virtually any college or university in the world, as well as many governmental institutes and

  10. Research Networking Systems: The State of Adoption at Institutions Aiming to Augment Translational Research Infrastructure

    PubMed Central

    Obeid, Jihad S; Johnson, Layne M; Stallings, Sarah; Eichmann, David

    2015-01-01

    Fostering collaborations across multiple disciplines within and across institutional boundaries is becoming increasingly important with the growing emphasis on translational research. As a result, Research Networking Systems that facilitate discovery of potential collaborators have received significant attention by institutions aiming to augment their research infrastructure. We have conducted a survey to assess the state of adoption of these new tools at the Clinical and Translational Science Award (CTSA) funded institutions. Survey results demonstrate that most CTSA funded institutions have either already adopted or were planning to adopt one of several available research networking systems. Moreover a good number of these institutions have exposed or plan to expose the data on research expertise using linked open data, an established approach to semantic web services. Preliminary exploration of these publically-available data shows promising utility in assessing cross-institutional collaborations. Further adoption of these technologies and analysis of the data are needed, however, before their impact on cross-institutional collaboration in research can be appreciated and measured. PMID:26491707

  11. The Function Biomedical Informatics Research Network Data Repository.

    PubMed

    Keator, David B; van Erp, Theo G M; Turner, Jessica A; Glover, Gary H; Mueller, Bryon A; Liu, Thomas T; Voyvodic, James T; Rasmussen, Jerod; Calhoun, Vince D; Lee, Hyo Jong; Toga, Arthur W; McEwen, Sarah; Ford, Judith M; Mathalon, Daniel H; Diaz, Michele; O'Leary, Daniel S; Jeremy Bockholt, H; Gadde, Syam; Preda, Adrian; Wible, Cynthia G; Stern, Hal S; Belger, Aysenil; McCarthy, Gregory; Ozyurt, Burak; Potkin, Steven G

    2016-01-01

    The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data. PMID:26364863

  12. Lambdastation: a forwarding and admission control service to interface production network facilities with advanced research network paths

    SciTech Connect

    DeMar, Philip; Petravick, Don; /Fermilab

    2004-12-01

    Over the past several years, there has been a great deal of research effort and funding put into the deployment of optical-based, advanced technology wide-area networks. Fermilab and CalTech have initiated a project to enable our production network facilities to exploit these advanced research network facilities. Our objective is to forward designated data transfers across these advanced wide area networks on a per-flow basis, making use our capacious production-use storage systems connected to the local campus network. To accomplish this, we intend to develop a dynamically provisioned forwarding service that would provide alternate path forwarding onto available wide area advanced research networks. The service would dynamically reconfigure forwarding of specific flows within our local production-use network facilities, as well as provide an interface to enable applications to utilize the service. We call this service LambdaStation. If one envisions wide area optical network paths as high bandwidth data railways, then LambdaStation would functionally be the railroad terminal that regulates which flows at the local site get directed onto the high bandwidth data railways. LambdaStation is a DOE-funded SciDac research project in its very early stage of development.

  13. The Greater Plains Collaborative: a PCORnet Clinical Research Data Network.

    PubMed

    Waitman, Lemuel R; Aaronson, Lauren S; Nadkarni, Prakash M; Connolly, Daniel W; Campbell, James R

    2014-01-01

    The Greater Plains Collaborative (GPC) is composed of 10 leading medical centers repurposing the research programs and informatics infrastructures developed through Clinical and Translational Science Award initiatives. Partners are the University of Kansas Medical Center, Children's Mercy Hospital, University of Iowa Healthcare, the University of Wisconsin-Madison, the Medical College of Wisconsin and Marshfield Clinic, the University of Minnesota Academic Health Center, the University of Nebraska Medical Center, the University of Texas Health Sciences Center at San Antonio, and the University of Texas Southwestern Medical Center. The GPC network brings together a diverse population of 10 million people across 1300 miles covering seven states with a combined area of 679 159 square miles. Using input from community members, breast cancer was selected as a focus for cohort building activities. In addition to a high-prevalence disorder, we also selected a rare disease, amyotrophic lateral sclerosis.

  14. The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging.

    PubMed

    Ladiges, Warren; Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A; Ciol, Marcia A; Ritchey, Jerry; Liggitt, Denny

    2016-04-01

    Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations.

  15. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers.

    PubMed

    Dunnenberger, Henry M; Crews, Kristine R; Hoffman, James M; Caudle, Kelly E; Broeckel, Ulrich; Howard, Scott C; Hunkler, Robert J; Klein, Teri E; Evans, William E; Relling, Mary V

    2015-01-01

    Although the field of pharmacogenetics has existed for decades, practioners have been slow to implement pharmacogenetic testing in clinical care. Numerous publications describe the barriers to clinical implementation of pharmacogenetics. Recently, several freely available resources have been developed to help address these barriers. In this review, we discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of patients. Array-based preemptive testing includes a large number of relevant pharmacogenes that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to be available prior to any prescribing decision so that genomic variation may be considered as an inherent patient characteristic in the planning of therapy. This review describes the common elements among programs that have implemented preemptive genotyping and highlights key processes for implementation, including clinical decision support.

  16. Controlled ovarian hyperstimulation pharmacogenetics: a simplified model to genetically dissect estrogen-related diseases.

    PubMed

    Morón, Francisco Jesús; Galán, José Jorge; Ruiz, Agustín

    2007-07-01

    The application of pharmacogenetics and pharmacogenomics to assisted reproductive techniques will help clinicians to improve the efficacy of hormone treatments that are being routinely applied during assisted reproductive technique protocols. Genetic markers involving controlled ovarian hyperstimulation pharmacogenetics are being isolated within follicle-stimulating hormone and estrogen receptor signaling pathways using the candidate gene approach. Furthermore, the information obtained during controlled ovarian hyperstimulation pharmacogenetics studies could be applied to other estrogen-related diseases, such as osteoporosis, breast cancer, essential hypertension and many other diseases related to estrogen production or its mechanism of action. The theory that estrogen-related diseases may share some risk factors with controlled ovarian hyperstimulation efficacy, and side effects linked to genetic markers, is discussed.

  17. Design and Evaluation of a Widget-Based Dashboard for Awareness Support in Research Networks

    ERIC Educational Resources Information Center

    Reinhardt, Wolfgang; Mletzko, Christian; Drachsler, Hendrik; Sloep, Peter B.

    2014-01-01

    In this article, we describe the rationale, design and evaluation of a widget-based dashboard to support scholars' awareness of their Research Networks. We introduce the concept of a Research Network and discuss Personal Research Environments that are built of as a development parallel to Personal Learning Environments. Based on the results…

  18. The National Research and Education Network (NREN): Promise of New Information Environments. ERIC Digest.

    ERIC Educational Resources Information Center

    Bishop, Ann P.

    This digest describes proposed legislation for the implementation of the National Research and Education Network (NREN). Issues and implications for teachers, students, researchers, and librarians are suggested and the emergence of the electronic network as a general communication and research tool is described. Developments in electronic…

  19. Research and Simulation on Application of the Mobile IP Network

    NASA Astrophysics Data System (ADS)

    Yibing, Deng; Wei, Hu; Minghui, Li; Feng, Gao; Junyi, Shen

    The paper analysed the mobile node, home agent, and foreign agent of mobile IP network firstly, some key technique, such as mobile IP network basical principle, protocol work principle, agent discovery, registration, and IP packet transmission, were discussed. Then a network simulation model was designed, validating the characteristic of mobile IP network, and some advantages, which were brought by mobile network, were testified. Finally, the conclusion is gained: mobile IP network could realize the expectation of consumer that they can communicate with others anywhere.

  20. The Deep Space Network: An instrument for radio astronomy research

    NASA Technical Reports Server (NTRS)

    Renzetti, N. A.; Levy, G. S.; Kuiper, T. B. H.; Walken, P. R.; Chandlee, R. C.

    1988-01-01

    The NASA Deep Space Network operates and maintains the Earth-based two-way communications link for unmanned spacecraft exploring the solar system. It is NASA's policy to also make the Network's facilities available for radio astronomy observations. The Network's microwave communication systems and facilities are being continually upgraded. This revised document, first published in 1982, describes the Network's current radio astronomy capabilities and future capabilities that will be made available by the ongoing Network upgrade. The Bibliography, which includes published papers and articles resulting from radio astronomy observations conducted with Network facilities, has been updated to include papers to May 1987.

  1. Pharmacogenetics and personalized treatment of type 2 diabetes

    PubMed Central

    Semiz, Sabina; Dujic, Tanja; Causevic, Adlija

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a worldwide epidemic with considerable health and economic consequences. T2DM patients are often treated with more than one drug, including oral antidiabetic drugs (OAD) and drugs used to treat diabetic complications, such as dyslipidemia and hypertension. If genetic testing could be employed to predict treatment outcome, appropriate measures could be taken to treat T2DM more efficiently. Here we provide a review of pharmacogenetic studies focused on OAD and a role of common drug-metabolizing enzymes (DME) and drug-transporters (DT) variants in therapy outcomes. For example, genetic variations of several membrane transporters, including SLC22A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM. Furthermore, cytochrome P450 (CYP) enzymes are implicated in variation of sulphonylurea and meglitinide metabolism. Additional variants related to drug target and diabetes risk genes have been also linked to interindividual differences in the efficacy and toxicity of OAD. Thus, in addition to promoting safe and cost-effective individualized diabetes treatment, pharmacogenomics has a great potential to complement current efforts to optimize treatment of diabetes and lead towards its effective and personalized care. PMID:23894862

  2. Pharmacogenetics and personalized treatment of type 2 diabetes.

    PubMed

    Semiz, Sabina; Dujic, Tanja; Causevic, Adlija

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a worldwide epidemic with considerable health and economic consequences. T2DM patients are often treated with more than one drug, including oral antidiabetic drugs (OAD) and drugs used to treat diabetic complications, such as dyslipidemia and hypertension. If genetic testing could be employed to predict treatment outcome, appropriate measures could be taken to treat T2DM more efficiently. Here we provide a review of pharmacogenetic studies focused on OAD and a role of common drug-metabolizing enzymes (DME) and drug-transporters (DT) variants in therapy outcomes. For example, genetic variations of several membrane transporters, including SLC2A1/2 and SLC47A1/2 genes, are implicated in the highly variable glycemic response to metformin, a first-line drug used to treat newly diagnosed T2DM. Furthermore, cytochrome P450 (CYP) enzymes are implicated in variation of sulphonylurea and meglitinide metabolism. Additional variants related to drug target and diabetes risk genes have been also linked to interindividual differences in the efficacy and toxicity of OAD. Thus, in addition to promoting safe and cost-effective individualized diabetes treatment, pharmacogenomics has a great potential to complement current efforts to optimize treatment of diabetes and lead towards its effective and personalized care. PMID:23894862

  3. Undetected Toxicity Risk in Pharmacogenetic Testing for Dihydropyrimidine Dehydrogenase

    PubMed Central

    Falvella, Felicia Stefania; Caporale, Marta; Cheli, Stefania; Martinetti, Antonia; Berenato, Rosa; Maggi, Claudia; Niger, Monica; Ricchini, Francesca; Bossi, Ilaria; Di Bartolomeo, Maria; Sottotetti, Elisa; Bernardi, Francesca Futura; de Braud, Filippo; Clementi, Emilio; Pietrantonio, Filippo

    2015-01-01

    Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%–30% of patients. Dihydropyrimidine dehydrogenase (DPD), a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene (DPYD) polymorphisms are associated with decreased enzyme activity and increased risk of fluoropyrimidine-related toxicity. In patients carrying non-functional DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T), fluoropyrimidines should be avoided or reduced according to the patients’ homozygous or heterozygous status, respectively. For other common DPYD variants (c.496A>G, c.1129-5923C>G, c.1896T>C), conflicting data are reported and their use in clinical practice still needs to be validated. The high frequency of DPYD polymorphism and the lack of large prospective trials may explain differences in studies’ results. The epigenetic regulation of DPD expression has been recently investigated to explain the variable activity of the enzyme. DPYD promoter methylation and its regulation by microRNAs may affect the toxicity risk of fluoropyrimidines. The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer. PMID:25906475

  4. Pharmacogenetic biomarkers: cytochrome P450 3A5.

    PubMed

    MacPhee, Iain A M

    2012-09-01

    The immunosuppressive drugs used for solid organ transplantation all have a narrow therapeutic index with wide variation between individuals in the blood concentration achieved by a given dose. Therapeutic drug monitoring is employed routinely but may not allow optimisation of drug exposure during the critical period two to three days following transplantation. A key factor in the inter-individual variability for tacrolimus, and probably sirolimus, is whether an individual is genetically predicted to express the drug metabolising enzyme cytochrome P450 3A5 (CYP3A5). Individuals predicted to express CYP3A5 by possession of at least one wild-type CYP3A5*1 allele require 1.5-2 times higher doses of tacrolimus to achieve target blood concentrations than individuals homozygous for the CYP3A5*3 allele who are functional non-expressers of CYP3A5. Planning the initial tacrolimus dose based on the CYP3A5 genotype has been shown to allow more rapid achievement of target blood concentrations after transplantation than a standard dose given to all patients. However, it remains to be demonstrated that use of this approach as an adjunct to therapeutic drug monitoring can reduce either efficacy failure (transplant rejection) or toxicity. Use of a pharmacogenetic approach to dosing sirolimus awaits testing and it is unlikely to be useful for ciclosporin or everolimus.

  5. Proposed Development of NASA Glenn Research Center's Aeronautical Network Research Simulator

    NASA Technical Reports Server (NTRS)

    Nguyen, Thanh C.; Kerczewski, Robert J.; Wargo, Chris A.; Kocin, Michael J.; Garcia, Manuel L.

    2004-01-01

    Accurate knowledge and understanding of data link traffic loads that will have an impact on the underlying communications infrastructure within the National Airspace System (NAS) is of paramount importance for planning, development and fielding of future airborne and ground-based communications systems. Attempting to better understand this impact, NASA Glenn Research Center (GRC), through its contractor Computer Networks & Software, Inc. (CNS, Inc.), has developed an emulation and test facility known as the Virtual Aircraft and Controller (VAC) to study data link interactions and the capacity of the NAS to support Controller Pilot Data Link Communications (CPDLC) traffic. The drawback of the current VAC test bed is that it does not allow the test personnel and researchers to present a real world RF environment to a complex airborne or ground system. Fortunately, the United States Air Force and Navy Avionics Test Commands, through its contractor ViaSat, Inc., have developed the Joint Communications Simulator (JCS) to provide communications band test and simulation capability for the RF spectrum through 18 GHz including Communications, Navigation, and Identification and Surveillance functions. In this paper, we are proposing the development of a new and robust test bed that will leverage on the existing NASA GRC's VAC and the Air Force and Navy Commands JCS systems capabilities and functionalities. The proposed NASA Glenn Research Center's Aeronautical Networks Research Simulator (ANRS) will combine current Air Traffic Control applications and physical RF stimulation into an integrated system capable of emulating data transmission behaviors including propagation delay, physical protocol delay, transmission failure and channel interference. The ANRS will provide a simulation/stimulation tool and test bed environment that allow the researcher to predict the performance of various aeronautical network protocol standards and their associated waveforms under varying

  6. Co-authorship network analysis in health research: method and potential use.

    PubMed

    Fonseca, Bruna de Paula Fonseca E; Sampaio, Ricardo Barros; Fonseca, Marcus Vinicius de Araújo; Zicker, Fabio

    2016-04-30

    Scientific collaboration networks are a hallmark of contemporary academic research. Researchers are no longer independent players, but members of teams that bring together complementary skills and multidisciplinary approaches around common goals. Social network analysis and co-authorship networks are increasingly used as powerful tools to assess collaboration trends and to identify leading scientists and organizations. The analysis reveals the social structure of the networks by identifying actors and their connections. This article reviews the method and potential applications of co-authorship network analysis in health. The basic steps for conducting co-authorship studies in health research are described and common network metrics are presented. The application of the method is exemplified by an overview of the global research network for Chikungunya virus vaccines.

  7. Co-authorship network analysis in health research: method and potential use.

    PubMed

    Fonseca, Bruna de Paula Fonseca E; Sampaio, Ricardo Barros; Fonseca, Marcus Vinicius de Araújo; Zicker, Fabio

    2016-01-01

    Scientific collaboration networks are a hallmark of contemporary academic research. Researchers are no longer independent players, but members of teams that bring together complementary skills and multidisciplinary approaches around common goals. Social network analysis and co-authorship networks are increasingly used as powerful tools to assess collaboration trends and to identify leading scientists and organizations. The analysis reveals the social structure of the networks by identifying actors and their connections. This article reviews the method and potential applications of co-authorship network analysis in health. The basic steps for conducting co-authorship studies in health research are described and common network metrics are presented. The application of the method is exemplified by an overview of the global research network for Chikungunya virus vaccines. PMID:27138279

  8. GMES Initial Operations - Network for Earth Observation Research Training (GIONET)

    NASA Astrophysics Data System (ADS)

    Nicolas-Perea, V.; Balzter, H.

    2012-12-01

    GMES Initial Operations - Network for Earth Observation Research Training (GIONET) is a Marie Curie funded project that aims to establish the first of a kind European Centre of Excellence for Earth Observation Research Training. GIONET is a partnership of leading Universities, research institutes and private companies from across Europe aiming to cultivate a community of early stage researchers in the areas of optical and radar remote sensing skilled for the emerging GMES land monitoring services during the GMES Initial Operations period (2011-2013) and beyond. GIONET is expected to satisfy the demand for highly skilled researchers and provide personnel for operational phase of the GMES and monitoring and emergency services. It will achieve this by: -Providing postgraduate training in Earth Observation Science that exposes students to different research disciplines and complementary skills, providing work experiences in the private and academic sectors, and leading to a recognized qualification (Doctorate). -Enabling access to first class training in both fundamental and applied research skills to early-stage researchers at world-class academic centers and market leaders in the private sector. -Building on the experience from previous GMES research and development projects in the land monitoring and emergency information services. The training program through supervised research focuses on 14 research topics (each carried out by an Early Stage Researchers based in one of the partner organization) divided in 5 main areas: Forest monitoring: Global biomass information systems Forest Monitoring of the Congo Basin using Synthetic Aperture radar (SAR) Multi-concept Earth Observation Capabilities for Biomass Mapping and Change Detection: Synergy of Multi-temporal and Multi-frequency Interferometric Radar and Optical Satellite Data Land cover and change: Multi-scale Remote Sensing Synergy for Land Process Studies: from field Spectrometry to Airborne Hyperspectral and

  9. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

    PubMed

    Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A; Barnes, Michael R; Li, Xiaohui; Warren, Helen R; Chasman, Daniel I; Zhou, Kaixin; Arsenault, Benoit J; Donnelly, Louise A; Wiggins, Kerri L; Avery, Christy L; Griffin, Paula; Feng, QiPing; Taylor, Kent D; Li, Guo; Evans, Daniel S; Smith, Albert V; de Keyser, Catherine E; Johnson, Andrew D; de Craen, Anton J M; Stott, David J; Buckley, Brendan M; Ford, Ian; Westendorp, Rudi G J; Slagboom, P Eline; Sattar, Naveed; Munroe, Patricia B; Sever, Peter; Poulter, Neil; Stanton, Alice; Shields, Denis C; O'Brien, Eoin; Shaw-Hawkins, Sue; Chen, Y-D Ida; Nickerson, Deborah A; Smith, Joshua D; Dubé, Marie Pierre; Boekholdt, S Matthijs; Hovingh, G Kees; Kastelein, John J P; McKeigue, Paul M; Betteridge, John; Neil, Andrew; Durrington, Paul N; Doney, Alex; Carr, Fiona; Morris, Andrew; McCarthy, Mark I; Groop, Leif; Ahlqvist, Emma; Bis, Joshua C; Rice, Kenneth; Smith, Nicholas L; Lumley, Thomas; Whitsel, Eric A; Stürmer, Til; Boerwinkle, Eric; Ngwa, Julius S; O'Donnell, Christopher J; Vasan, Ramachandran S; Wei, Wei-Qi; Wilke, Russell A; Liu, Ching-Ti; Sun, Fangui; Guo, Xiuqing; Heckbert, Susan R; Post, Wendy; Sotoodehnia, Nona; Arnold, Alice M; Stafford, Jeanette M; Ding, Jingzhong; Herrington, David M; Kritchevsky, Stephen B; Eiriksdottir, Gudny; Launer, Leonore J; Harris, Tamara B; Chu, Audrey Y; Giulianini, Franco; MacFadyen, Jean G; Barratt, Bryan J; Nyberg, Fredrik; Stricker, Bruno H; Uitterlinden, André G; Hofman, Albert; Rivadeneira, Fernando; Emilsson, Valur; Franco, Oscar H; Ridker, Paul M; Gudnason, Vilmundur; Liu, Yongmei; Denny, Joshua C; Ballantyne, Christie M; Rotter, Jerome I; Adrienne Cupples, L; Psaty, Bruce M; Palmer, Colin N A; Tardif, Jean-Claude; Colhoun, Helen M; Hitman, Graham; Krauss, Ronald M; Wouter Jukema, J; Caulfield, Mark J

    2014-10-28

    Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

  10. An Analysis for the Use of Research and Education Networks and Commercial Network Vendors in Support of Space Based Mission Critical and Non-Critical Networking

    NASA Technical Reports Server (NTRS)

    Bradford, Robert N.

    2002-01-01

    Currently, and in the past, dedicated communication circuits and "network services" with very stringent performance requirements are being used to support manned and unmanned mission critical ground operations at GSFC, JSC, MSFC, KSC and other NASA facilities. Because of the evolution of network technology, it is time to investigate using other approaches to providing mission services for space ground operations. The current NASA approach is not in keeping with the evolution of network technologies. In the past decade various research and education networks dedicated to scientific and educational endeavors have emerged, as well as commercial networking providers, that employ advanced networking technologies. These technologies have significantly changed networking in recent years. Significant advances in network routing techniques, various topologies and equipment have made commercial networks very stable and virtually error free. Advances in Dense Wave Division Multiplexing will provide tremendous amounts of bandwidth for the future. The question is: Do these networks, which are controlled and managed centrally, provide a level of service that equals the stringent NASA performance requirements. If they do, what are the implication(s) of using them for critical space based ground operations as they are, without adding high cost contractual performance requirements? A second question is the feasibility of applying the emerging grid technology in space operations. Is it feasible to develop a Space Operations Grid and/or a Space Science Grid? Since these network's connectivity is substantial, both nationally and internationally, development of these sorts of grids may be feasible. The concept of research and education networks has evolved to the international community as well. Currently there are international RENs connecting the US in Chicago to and from Europe, South America, Asia and the Pacific rim, Russia and Canada. And most countries in these areas have their

  11. The Seniors Health Research Transfer Network Knowledge Network Model: system-wide implementation for health and healthcare of seniors.

    PubMed

    Chambers, Larry W; Luesby, Deirdre; Brookman, Catherine; Harris, Megan; Lusk, Elizabeth

    2010-01-01

    The Ontario Seniors Health Research Transfer Network (SHRTN) aims to improve the health of older adults through increasing the knowledge capacity of 850 community care agencies and 620 long-term care homes. The SHRTN includes caregivers, researchers, policy makers, administrators, educators, and organizations. The SHRTN comprises communities of practice, a library service, a network of 7 research institutes, and local implementation teams. The SHRTN combines face-to-face meetings with information technology to promote change at the client care level in organizational and provincial policies and in the promotion of health services research.

  12. Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

    PubMed Central

    Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

    2013-01-01

    Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

  13. GIONET (GMES Initial Operations Network for Earth Observation Research Training)

    NASA Astrophysics Data System (ADS)

    Nicolas, V.; Balzter, H.

    2013-12-01

    GMES Initial Operations - Network for Earth Observation Research Training (GIONET) is a Marie Curie funded project that aims to establish the first of a kind European Centre of Excellence for Earth Observation Research Training. Copernicus (previously known as GMES (Global Monitoring for Environment and Security) is a joint undertaking of the European Space Agency and the European Commission. It develops fully operational Earth Observation monitoring services for a community of end users from the public and private sector. The first services that are considered fully operational are the land monitoring and emergency monitoring core services. In GIONET, 14 early stage researchers are being trained at PhD level in understanding the complex physical processes that determine how electromagnetic radiation interacts with the atmosphere and the land surface ultimately form the signal received by a satellite. In order to achieve this, the researchers are based in industry and universities across Europe, as well as receiving the best technical training and scientific education. The training programme through supervised research focuses on 14 research topics. Each topic is carried out by an Early Stage Researcher based in one of the partner organisations and is expected to lead to a PhD degree. The 14 topics are grouped in 5 research themes: Forest monitoring Land cover and change Coastal zone and freshwater monitoring Geohazards and emergency response Climate adaptation and emergency response The methods developed and used in GIONET are as diverse as its research topics. GIONET has already held two summer schools; one at Friedrich Schiller University in Jena (Germany), on 'New operational radar satellite applications: Introduction to SAR, Interferometry and Polarimetry for Land Surface Mapping'. The 2nd summer school took place last September at the University of Leicester (UK )on 'Remote sensing of land cover and forest in GMES'. The next Summer School in September 2013

  14. Patient Informed Governance of Distributed Research Networks: Results and Discussion from Six Patient Focus Groups

    PubMed Central

    Mamo, Laura A.; Browe, Dennis K.; Logan, Holly C.; Kim, Katherine K.

    2013-01-01

    Understanding how to govern emerging distributed research networks is essential to their success. Distributed research networks aggregate patient medical data from many institutions leaving data within the local provider security system. While much is known about patients’ views on secondary medical research, little is known about their views on governance of research networks. We conducted six focus groups with patients from three medical centers across the U.S. to understand their perspectives on privacy, consent, and ethical concerns of sharing their data as part of research networks. Participants positively endorsed sharing their health data with these networks believing that doing so could advance healthcare knowledge. However, patients expressed several concerns regarding security and broader ethical issues such as commercialism, public benefit, and social responsibility. We suggest that network governance guidelines move beyond strict technical requirements and address wider socio-ethical concerns by fully including patients in governance processes. PMID:24551383

  15. Patient informed governance of distributed research networks: results and discussion from six patient focus groups.

    PubMed

    Mamo, Laura A; Browe, Dennis K; Logan, Holly C; Kim, Katherine K

    2013-01-01

    Understanding how to govern emerging distributed research networks is essential to their success. Distributed research networks aggregate patient medical data from many institutions leaving data within the local provider security system. While much is known about patients' views on secondary medical research, little is known about their views on governance of research networks. We conducted six focus groups with patients from three medical centers across the U.S. to understand their perspectives on privacy, consent, and ethical concerns of sharing their data as part of research networks. Participants positively endorsed sharing their health data with these networks believing that doing so could advance healthcare knowledge. However, patients expressed several concerns regarding security and broader ethical issues such as commercialism, public benefit, and social responsibility. We suggest that network governance guidelines move beyond strict technical requirements and address wider socio-ethical concerns by fully including patients in governance processes.

  16. Mapping the Field of Educational Administration Research: A Journal Citation Network Analysis

    ERIC Educational Resources Information Center

    Wang, Yinying; Bowers, Alex J.

    2016-01-01

    Purpose: The purpose of this paper is to uncover how knowledge is exchanged and disseminated in the educational administration research literature through the journal citation network. Design/ Methodology/Approach: Drawing upon social network theory and citation network studies in other disciplines, the authors constructed an educational…

  17. Social Networking as a Recruitment Strategy for Mexican American Families in Community Health Research.

    ERIC Educational Resources Information Center

    Hooks, Paul C.; And Others

    1986-01-01

    Reports use of social networking to recruit 64 Mexican-American children for an assessment of diet and exercise habits. Describes friendship, social, consanguineal, and coparenthood networks. Compares results of direct contact versus network contact. Discusses implications for recruiting ethnic groups for research. (LFL)

  18. Electronic Data Collection Options for Practice-Based Research Networks

    PubMed Central

    Pace, Wilson D.; Staton, Elizabeth W.

    2005-01-01

    PURPOSE We wanted to describe the potential benefits and problems associated with selected electronic methods of collecting data within practice-based research networks (PBRNs). METHODS We considered a literature review, discussions with PBRN researchers, industry information, and personal experience. This article presents examples of selected PBRNs’ use of electronic data collection. RESULTS Collecting research data in the geographically dispersed PBRN environment requires considerable coordination to ensure completeness, accuracy, and timely transmission of the data, as well as a limited burden on the participants. Electronic data collection, particularly at the point of care, offers some potential solutions. Electronic systems allow use of transparent decision algorithms and improved data entry and data integrity. These systems may improve data transfer to the central office as well as tracking systems for monitoring study progress. PBRNs have available to them a wide variety of electronic data collection options, including notebook computers, tablet PCs, personal digital assistants (PDAs), and browser-based systems that operate independent of or over the Internet. Tablet PCs appear particularly advantageous for direct patient data collection in an office environment. PDAs work well for collecting defined data elements at the point of care. Internet-based systems work well for data collection that can be completed after the patient visit, as most primary care offices do not support Internet connectivity in examination rooms. CONCLUSIONS When planning to collect data electronically, it is important to match the electronic data collection method to the study design. Focusing an inappropriate electronic data collection method onto users can interfere with accurate data gathering and may also anger PBRN members. PMID:15928215

  19. Improving diversity in cancer research trials: the story of the Cancer Disparities Research Network.

    PubMed

    Simon, Melissa A; de la Riva, Erika E; Bergan, Raymond; Norbeck, Carrie; McKoy, June M; Kulesza, Piotr; Dong, XinQi; Schink, Julian; Fleisher, Linda

    2014-06-01

    The participation of racial and ethnic minorities and underserved populations in clinical trials is a critical link between scientific innovation and improvements in health care delivery and health outcomes. However, these population groups continue to be underrepresented in research. We describe the development of the Cancer Disparities Research Network (CDRN) to improve minority and underserved populations' participation in biobanking research. Between February and October 2011, we conducted a regional assessment to identify challenges and opportunities for cancer trials and biobanking research across the CDRN. Representatives from ten CDRN biorepository facilities completed an online survey assessing their facilities' minority biospecimen collection, biobanking practices, and education/outreach initiatives. Representatives of eight facilities also participated in stakeholder interviews. The majority (70%) of facilities reported that specimens were available for research, although only one tenth of these specimens were from non-White patients. Most facilities collected a patient's age, gender, race, medical history, and ethnicity with samples; however, less than half also collected family health history, education level, household income, or primary language spoken. In addition, few institutions collected Asian or Hispanic subgroup information. Only a few reported biospecimen collection outreach programs specifically targeting minority and underserved populations. Biospecimen directors and administrators indicated that funding, biospecimen sharing procedures, and standardization barriers limited their facilities from collaborating in biospecimen collection programs, despite their great interest. These findings suggest that the CDRN can provide opportunities for collaboration, resource sharing, and fostering of research ideas to address cancer disparities in biospecimen research. PMID:24519744

  20. [AFNET. A translational research network develops into an academic research organization].

    PubMed

    Kirchhof, Paulus; Goette, Andreas; Näbauer, Michael; Schotten, Ulrich

    2016-04-01

    "The whole is greater than the sum of its parts" (Aristotle).Atrial fibrillation (AF) is the most common sustained arrhythmia and affects 1-2 % of the population in developed countries, especially the elderly. We expect that the prevalence of AF will double in the next few decades. The last decades have seen important improvements in the management of atrial fibrillation, but many questions remain regarding the optimal diagnosis and management of the condition. The German Atrial Fibrillation NETwork (AFNET) was one of three cardiovascular competence networks in medicine funded by the German Ministry of Education and Research between 2003-2014. AFNET has contributed to the understanding of atrial fibrillation, and AFNET-led studies have led to improved clinical practices and practice guidelines in Germany and in Europe. This work has been expanded and is continuing in the AFNET association (AFNET e. V.). The AFNET association, founded in 2010 and continuing to this day, has developed into a small but fully formed academic research organisation that conducts investigator-initiated clinical trials as the responsible sponsor in Germany, Europe, and beyond. The AFNET association currently cooperates with EHRA (The European Heart Rhythm Association), ESC (The European Society of Cardiology) and DZHK (The German Centre for Cardiovascular Research) and receives funding from the European Union to generate evidence that can in the future lead to better prevention and management of AF.

  1. The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States

    PubMed Central

    Tzimenatos, Leah; Kim, Emily; Kuppermann, Nathan

    2014-01-01

    In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network (PECARN), and highlight some of the important accomplishments since its inception. We also describe the network’s strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future, but the growth of research in emergency medical services for children in general.

  2. Convening a Network within the European Conference on Educational Research: A History of the Social Justice and Intercultural Education Network

    ERIC Educational Resources Information Center

    Bhatti, Ghazala; Leeman, Yvonne

    2011-01-01

    The experience of initiating and sustaining a research-based dialogue on social justice and intercultural education in Europe requires both flexibility and focus. This article highlights the challenges facing convenors of one network, who wish to include researchers from diverse backgrounds, while at the same time enhancing the academic quality of…

  3. Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.

    PubMed

    Cusato, Jessica; Allegra, Sarah; De Nicolò, Amedeo; Boglione, Lucio; Fatiguso, Giovanna; Abdi, Adnan Mohamed; Cariti, Giuseppe; Di Perri, Giovanni; D'Avolio, Antonio

    2015-06-01

    Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs. The median S isomer PBMC/plasma concentration ratio was 28.59. A significant positive correlation was found between plasma and PBMC S isomer concentrations. ABCB1 1236, SLC28A2 124 and IL28B rs12979860 SNPs were associated with the S isomer PBMC/plasma concentration ratio. In regression models, S isomer plasma levels and FokI polymorphism were able to predict S isomer intracellular exposure, whereas SNPs in AKR1, BCRP1 and SLC28A2 predicted the S isomer PBMC/plasma concentration ratio. No similar data regarding BOC pharmacogenetics and pharmacokinetics have been published previously. This study adds a novel and useful overview of the pharmacological properties of this drug. PMID:25836019

  4. Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.

    PubMed

    Cusato, Jessica; Allegra, Sarah; De Nicolò, Amedeo; Boglione, Lucio; Fatiguso, Giovanna; Abdi, Adnan Mohamed; Cariti, Giuseppe; Di Perri, Giovanni; D'Avolio, Antonio

    2015-06-01

    Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs. The median S isomer PBMC/plasma concentration ratio was 28.59. A significant positive correlation was found between plasma and PBMC S isomer concentrations. ABCB1 1236, SLC28A2 124 and IL28B rs12979860 SNPs were associated with the S isomer PBMC/plasma concentration ratio. In regression models, S isomer plasma levels and FokI polymorphism were able to predict S isomer intracellular exposure, whereas SNPs in AKR1, BCRP1 and SLC28A2 predicted the S isomer PBMC/plasma concentration ratio. No similar data regarding BOC pharmacogenetics and pharmacokinetics have been published previously. This study adds a novel and useful overview of the pharmacological properties of this drug.

  5. Pharmacogenetic determinants of immediate and delayed reactions of drug hypersensitivity.

    PubMed

    Guéant, J L; Guéant-Rodriguez, R M; Gastin, I Aimone; Cornejo-García, J A; Viola, M; Barbaud, A; Mertes, P M; Blanca, M; Romano, A

    2008-01-01

    Drug allergy refers to a hypersensitivity reaction for which either an IgE or T-cell-mediated mechanism is demonstrated. The recognition of the drug by B and T cells is influenced by variants of HLA genes. The genetic factors involved in IgE-mediated mechanisms have been studied mainly in beta-lactam reactions, and they appear to be related to human leukocyte antigen presentation (HLA A2 and DRw52), TNFA -308G>A, class switching to IgE by B cells (variants of IL-13 and of IL-4RA), and expression of IgE receptors on target cells (variant of the FcepsilonRIbeta gene). Delayed T-cell-mediated reactions are also associated with HLA alleles. Studies have reported an association of HLA-B*1502 and HLA-B*5801 in patients with the Stevens-Johnson syndrome or toxic epidermal necrolysis provoked by carbamazepine, as well as of HLA-B*5701 with abacavir hypersensitivity. HLA-B*5701 seems to be a strong predictor in whites, but not in Hispanics or Africans. Carbamazepine hypersensitivity is also influenced by gene variants of cytochrome P450 enzymes on the generation of reactive metabolites, while CYP2C9*2 and CYP2C9*3 polymorphisms influence the bioactivation of sulfamethoxazole in prohapten. Pharmacogenetic studies on aspirin hypersensitivity have identified distinct types of predictors, such as HLA genotypes, a polymorphism in the promoter of the FcepsilonRIalpha gene, and variants in genes of enzymes from the arachidonic acid pathway. In the future, identification of genetic predictors will benefit from genomewide association studies that also take ethnic differences into account. Ideally, predictors will help to prevent adverse reactions, as suggested by a recent study on the effectiveness of prospective HLA-B*5701 screening to prevent hypersensitivity reactions to abacavir in HIV patients. PMID:18991696

  6. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents

    PubMed Central

    Dos Santos-Júnior, Amilton; Henriques, Taciane Barbosa; de Mello, Maricilda Palandi; Della Torre, Osmar Henrique; Paes, Lúcia Arisaka; Ferreira-Neto, Adriana Perez; Sewaybricker, Letícia Esposito; Fontana, Thiago Salum; Celeri, Eloisa Helena Rubello Valler; Guerra-Júnior, Gil; Dalgalarrondo, Paulo

    2016-01-01

    Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8–20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. PMID:26880915

  7. Statistical performance of cladistic strategies for haplotype grouping in pharmacogenetics.

    PubMed

    Lunceford, Jared K; Liu, Nancy

    2008-12-10

    Haplotypes comprising multiple single nucleotide polymorphisms (SNPs) are popular covariates for capturing the key genetic variation present over a region of interest in the DNA sequence. Although haplotypes can provide a clearer assessment of genetic variation in a region than their component SNPs considered individually, the multi-allelic nature of haplotypes increases the complexity of the statistical models intended to discover association with outcomes of interest. Cladistic methods cluster haplotypes according to the estimates of their genealogical closeness and have been proposed recently as strategies for reducing model complexity and increasing power. Two examples are methods based on a haplotype nesting algorithm described by Templeton et al. (Genetics 1987; 117:343-351) and hierarchical clustering of haplotypes as described by Durrant et al. (Am. J. Hum. Genet. 2004; 75:35-43). In the context of assessing the pharmacogenetic effects of candidate genes, for which high-density SNP data have been gathered, we have conducted a simulation-based case study of the testing and estimation properties of two strategies based on Templeton's algorithm (TA), one being that described by Seltman et al. (Am. J. Hum. Genet. 2001; 68:1250-1263; Genet. Epidemiol. 2003; 25:48-58), as well as the method of Durrant et al. using data from a diabetes clinical trial. Even after adjusting for multiplicity, improvements in power can be realized using cladistic approaches with treatment group sizes in the range expected for standard trials, although these gains may be sensitive to the cladistic structure used. Differences in the relative performance of the cladistic approaches examined were observed with the clustering approach of Durrant et al. showing statistical properties superior to the methods based on TA.

  8. Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update.

    PubMed

    Teng, Renli

    2015-11-01

    Despite advancements in treatments for acute coronary syndromes over the last 10 years, they continue to be life-threatening disorders. Currently, the standard of treatment includes dual antiplatelet therapy consisting of aspirin plus a P2Y12 receptor antagonist. The thienopyridine class of P2Y12 receptor antagonists, clopidogrel and prasugrel, have demonstrated efficacy. However, their use is associated with several limitations, including the need for metabolic activation and irreversible P2Y12 receptor binding causing prolonged recovery of platelet function. In addition, response to clopidogrel is variable and efficacy is reduced in patients with certain genotypes. Although prasugrel is a more consistent inhibitor of platelet aggregation than clopidogrel, it is associated with an increased risk of life-threatening and fatal bleeding. Ticagrelor is an oral antiplatelet agent of the cyclopentyltriazolopyrimidine class and also acts through the P2Y12 receptor. In contrast to clopidogrel and prasugrel, ticagrelor does not require metabolic activation and binds rapidly and reversibly to the P2Y12 receptor. In light of new data, this review provides an update on the pharmacokinetic, pharmacodynamic and pharmacogenetic profiles of ticagrelor in different study populations. Recent studies report that no dose adjustment for ticagrelor is required on the basis of age, gender, ethnicity, severe renal impairment or mild hepatic impairment. The non-P2Y12 actions of ticagrelor are reviewed, showing indirect positive effects on cellular adenosine concentration and biological activity, by inhibition of equilibrative nucleoside transporter-1 independently of the P2Y12 receptor. CYP2C19 and ABCB1 genotypes do not appear to influence ticagrelor pharmacodynamics. A summary of drug interactions is also presented. PMID:26063049

  9. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents.

    PubMed

    Dos Santos-Júnior, Amilton; Henriques, Taciane Barbosa; de Mello, Maricilda Palandi; Della Torre, Osmar Henrique; Paes, Lúcia Arisaka; Ferreira-Neto, Adriana Perez; Sewaybricker, Letícia Esposito; Fontana, Thiago Salum; Celeri, Eloisa Helena Rubello Valler; Guerra-Júnior, Gil; Dalgalarrondo, Paulo

    2016-01-01

    Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. PMID:26880915

  10. OX1 and OX2 orexin/hypocretin receptor pharmacogenetics

    PubMed Central

    Thompson, Miles D.; Xhaard, Henri; Sakurai, Takeshi; Rainero, Innocenzo; Kukkonen, Jyrki P.

    2014-01-01

    Orexin/hypocretin peptide mutations are rare in humans. Even though human narcolepsy is associated with orexin deficiency, this is only extremely rarely due to mutations in the gene coding prepro-orexin, the precursor for both orexin peptides. In contrast, coding and non-coding variants of the OX1 and OX2 orexin receptors have been identified in many human populations; sometimes, these have been associated with disease phenotype, although most confer a relatively low risk. In most cases, these studies have been based on a candidate gene hypothesis that predicts the involvement of orexins in the relevant pathophysiological processes. In the current review, the known human OX1/HCRTR1 and OX2/HCRTR2 genetic variants/polymorphisms as well as studies concerning their involvement in disorders such as narcolepsy, excessive daytime sleepiness, cluster headache, polydipsia-hyponatremia in schizophrenia, and affective disorders are discussed. In most cases, the functional cellular or pharmacological correlates of orexin variants have not been investigated—with the exception of the possible impact of an amino acid 10 Pro/Ser variant of OX2 on orexin potency—leaving conclusions on the nature of the receptor variant effects speculative. Nevertheless, we present perspectives that could shape the basis for further studies. The pharmacology and other properties of the orexin receptor variants are discussed in the context of GPCR signaling. Since orexinergic therapeutics are emerging, the impact of receptor variants on the affinity or potency of ligands deserves consideration. This perspective (pharmacogenetics) is also discussed in the review. PMID:24834023

  11. Ethambutol plasma and intracellular pharmacokinetics: A pharmacogenetic study.

    PubMed

    Fatiguso, Giovanna; Allegra, Sarah; Calcagno, Andrea; Baietto, Lorena; Motta, Ilaria; Favata, Fabio; Cusato, Jessica; Bonora, Stefano; Perri, Giovanni Di; D'Avolio, Antonio

    2016-01-30

    We evaluated ethambutol plasma and intracellular pharmacokinetic according to single nucleotide polymorphisms in ABCB1, OATP1B1, PXR, VDR, CYP24A1 and CYP27B1 genes. Mycobacterium tubercolosis infected patients were enrolled. Standard weight-adjusted antitubercular treatment was administered intravenously for 2 weeks and then orally. Allelic discrimination was performed by real-time PCR. Ethambutol plasma and intracellular concentrations were measured by UPLC-MS/MS methods. Twenty-four patients were included. Considering weeks 2 and 4, median plasma Ctrough were 73 ng/mL and 247 ng/mL, intracellular Ctrough were 16,863 ng/mL and 13,535 ng/mL, plasma Cmax were 5627 ng/mL and 2229 ng/mL, intracellular Cmax were 133,830 ng/mL and 78,544 ng/mL. At week 2, ABCB1 3435 CT/TT (p=0.023) and CYP24A1 8620 AG/GG (p=0.030) genotypes for plasma Ctrough, BsmI AA (p=0.036) for intracellular Ctrough and BsmI AA (p<0.001) and ApaI AA (p=0.048) for intracellular Cmax, remained in linear regression analysis as predictive factors. Concerning week 4 only ABCB1 3435 CT/TT (p=0.035) and Cdx2 AG/GG (p=0.004) genotypes for plasma Ctrough and BsmI AA (p=0.028) for plasma Cmax were retained in final regression model. We reveal, for the first time, the possible role of single nucleotide polymorphisms on ethambutol plasma and intracellular concentrations; this may further the potential use of pharmacogenetic for tailoring antitubercular treatment. PMID:26642947

  12. Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients

    PubMed Central

    Jeong, Sohyun; Kim, In-Wha; Oh, Kook-Hwan; Han, Nayoung; Joo, Kwon Wook; Kim, Hyo Jin; Oh, Jung Mi

    2016-01-01

    Background Secondary hyperparathyroidism (SHPT) is one of the major risk factors of morbidity and mortality in end-stage renal disease. Cinacalcet effectively controls SHPT without causing hypercalcemia and hyperphosphatemia. However, there is significant inter-individual response variance to cinacalcet treatment. Therefore, we aimed to evaluate the genetic effects related with parathyroid hormone regulation as factors for cinacalcet response variance. Methods Patients with a diagnosis of SHPT based on intact parathyroid hormone (iPTH) >300 pg/mL on dialysis were included in this study. They were over 18 years and have been treated by cinacalcet for more than 3 months. Responders and nonresponders were grouped by the serum iPTH changes. Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis. Results After adjusting for age, sex, and calcium level, CASR rs1042636 (odds ratio [OR]: 0.066, P=0.027) and rs1802757 (OR: 10.532, P=0.042) were associated with cinacalcet response. The association of haplotypes of CASR rs1042636, rs10190, and rs1802757; GCC (OR: 0.355, P=0.015); and ATT (OR: 2.769, P=0.014) with cinacalcet response was also significant. Conclusion We obtained supporting information of the associations between cinacalcet response and CASR polymorphisms. CASR single nucleotide polymorphisms (SNPs) rs1802757, rs1042636, and haplotypes of rs1042636, rs10190, and rs1802757 were significantly associated with cinacalcet response variance. PMID:27468225

  13. Pharmacogenetic Association Study of Warfarin Safety Endpoints in Puerto Ricans

    PubMed Central

    Valentín, Isa I.; Rivera, Giselle; Nieves-Plaza, Mariely; Cruz, Iadelisse; Renta, Jessica Y.; Cadilla, Carmen L.; Feliu, Juan F.; Seip, Richard L.; Ruaño, Gualberto; Duconge, Jorge

    2014-01-01

    Objective This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy). Methods We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 ±9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC 1 assays by Luminex. Event-free survival curves were estimated using the Kaplan–Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated. Results Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI : 1.0–6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found. Conclusion The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy. PMID:25244877

  14. Leveraging the Relationship: Knowledge Processes in School-University Research Networks of Master's Programmes

    ERIC Educational Resources Information Center

    Cornelissen, Frank; Daly, Alan J.; Liou, Yi-Hwa; Van Swet, Jacqueline; Beijaard, Douwe; Bergen, Theo C. M.

    2015-01-01

    This study investigated the way developing, sharing and using of research-based knowledge occurred in the school-university research network of a master's programme for in-service teachers in the Netherlands. Over a 10-month period, a combination of quantitative and qualitative network data was collected. Data were analysed at three network…

  15. Teaching the Geoweb: Interdisciplinary Undergraduate Research in Wireless Sensor Networks, Web Mapping, and Geospatial Data Management

    ERIC Educational Resources Information Center

    Abernathy, David

    2011-01-01

    This article addresses an effort to incorporate wireless sensor networks and the emerging tools of the Geoweb into undergraduate teaching and research at a small liberal arts college. The primary goal of the research was to identify the hardware, software, and skill sets needed to deploy a local sensor network, collect data, and transmit that data…

  16. 76 FR 46359 - Announcing the Nineteenth Public Meeting of the Crash Injury Research and Engineering Network...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    ... centers to enroll crash victims into the CIREN program. Engineering teams are led by mechanical engineers... Research and Engineering Network (CIREN) AGENCY: National Highway Traffic Safety Administration (NHTSA... members of the Crash Injury Research and Engineering Network. CIREN is a collaborative effort to...

  17. Establishing a Practice-Based Research Network: Lessons from the Massachusetts Experience

    ERIC Educational Resources Information Center

    Pulcini, Joyce; Sheetz, Anne; DeSisto, Marie

    2008-01-01

    This article describes the recently established Massachusetts School Nurse Research Network (MASNRN) which has a mission of establishing a practice-based research network (PBRN) comprised of a representative, collaborative group of professional school nurses, nurse academicians, and other interested parties for whom school health is a priority.…

  18. Understanding and Developing Inclusive Practices in Schools: A Collaborative Action Research Network

    ERIC Educational Resources Information Center

    Ainscow, Mel; Booth, Tony; Dyson, Alan

    2004-01-01

    This paper provides an account of the methodological lessons and emerging findings of a collaborative action research network in England. The Network involves teams of researchers from three universities in working alongside school and local education authority practitioners as they explore ways of developing more inclusive practices. The analysis…

  19. A Mixed-Methods Social Networks Study Design for Research on Transnational Families

    ERIC Educational Resources Information Center

    Bernardi, Laura

    2011-01-01

    This paper advocates the adoption of a mixed-methods research design to describe and analyze ego-centered social networks in transnational family research. Drawing on the experience of the "Social Networks Influences on Family Formation" project (2004-2005; see Bernardi, Keim, & von der Lippe, 2007a, 2007b), I show how the combined use of network…

  20. Using Action Research and Action Learning for Entrepreneurial Network Capability Development

    ERIC Educational Resources Information Center

    McGrath, Helen; O'Toole, Thomas

    2016-01-01

    This paper applies an action research (AR) design and action learning (AL) approach to network capability development in an entrepreneurial context. Recent research suggests that networks are a viable strategy for the entrepreneurial firm to overcome the liabilities associated with newness and smallness. However, a gap emerges as few, if any,…

  1. Research and realization of OADM technology in metro optical network

    NASA Astrophysics Data System (ADS)

    Ji, Yuefeng; Zhang, Jie; Sun, Yongmei; Gu, Wanyi; Ye, Bing; Zhao, Yong

    2001-10-01

    Optical Add/Drop Multiplexer (OADM) is an important network element. In the ring architecture, OADM can be introduced to make efficient use of network capacity, network protection, wavelength routing and many more good features. In this paper, an OADM with high performance realized by us is demonstrated. The key technical problem , solving method and design rule for the OADM are given. The experiment results of long distance transmission by use of the OADM are illuminated by some figure . It shows that the OADM realized by us is advanced, practical, reliable, and applied in China Advanced Info-Optical Network (CAINONet).

  2. Research on invulnerability of equipment support information network

    NASA Astrophysics Data System (ADS)

    Sun, Xiao; Liu, Bin; Zhong, Qigen; Cao, Zhiyi

    2013-03-01

    In this paper, the entity composition of equipment support information network is studied, and the network abstract model is built. The influence factors of the invulnerability of equipment support information network are analyzed, and the invulnerability capabilities under random attack are analyzed. According to the centrality theory, the materiality evaluation centralities of the nodes are given, and the invulnerability capabilities under selective attack are analyzed. Finally, the reasons that restrict the invulnerability of equipment support information network are summarized, and the modified principles and methods are given.

  3. A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?

    PubMed Central

    Baietto, Lorena; Corcione, Silvia; Pacini, Giovanni; Di Perri, Giovanni; D’Avolio#†, Antonio; Giuseppe De Rosa†, Francesco

    2014-01-01

    Drug bioavailability may vary greatly amongst individuals, affecting both efficacy and toxicity: in humans, genetic variations account for a relevant proportion of such variability. In the last decade the use of pharmacogenetics in clinical practice, as a tool to individualize treatment, has shown a different degree of diffusion in various clinical fields. In the field of infectious diseases, several studies identified a great number of associations between host genetic polymor-phisms and responses to antiretroviral therapy. For example, in patients treated with abacavir the screening for HLA-B*5701 before starting treatment is routine clinical practice and standard of care for all patients; efavirenz plasma levels are influenced by single nucleotide polymorphism (SNP) CYP2B6-516G> T (rs3745274). Regarding antibiotics, many studies investigated drug transporters involved in antibiotic bioavailability, especially for fluoroquinolones, cephalosporins, and antituberculars. To date, few data are available about pharmacogenetics of recently developed antibiotics such as tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene coding for proteins involved in antibiotics bioavailability, few data have been published. Increasing knowledge in the field of antibiotic pharmacogenetics could be useful to explain the high drug inter-patients variability and to individualize therapy. In this paper we reported an overview of pharmacokinetics, pharmacodynamics, and pharmacogenetics of antibiotics to underline the importance of an integrated approach in choosing the right dosage in clinical practice. PMID:24909419

  4. A Pharmacogenetic Screening Experiment Demonstrating Principles of Genetic Constitution on Drug Metabolism.

    ERIC Educational Resources Information Center

    Robbins, Doris K.; Wedlund, Peter J.

    1990-01-01

    A laboratory experiment designed to provide rapid, inexpensive student exposure to pharmacogenetics in drug elimination and patient therapy is described. The test, performed on students, determines expression of a drug metabolism enzyme following ingestion of a probe drug. (Author/MSE)

  5. “Getting off the Bus Closer to Your Destination”: Patients’ Views about Pharmacogenetic Testing

    PubMed Central

    Trinidad, Susan Brown; Coffin, Tara B; Fullerton, Stephanie M; Ralston, James; Jarvik, Gail P; Larson, Eric B

    2015-01-01

    Context: Pharmacogenetic testing, a form of precision medicine, has the potential to optimize medication choice and dosing. Yet, relatively little is known about the views of patients—particularly those with chronic psychiatric conditions—with respect to such testing. Objective: To explore patients’ beliefs and attitudes regarding pharmacogenetic testing, with the goal of informing policy development and implementation. Design: Qualitative study design using semistructured focus groups with adults enrolled in Group Health Cooperative, a large health maintenance organization in the Pacific Northwest. We conducted focus groups with patients prescribed antidepressants (pilot session plus 2 focus groups, n = 27); patients prescribed carbamazepine (2 focus groups, n = 17); and healthy patients (2 focus groups, n = 17). Results: Although participants understood the potential advantages of pharmacogenetic testing, many felt that the risks (discrimination, stigmatization, physician overreliance on genomic results, and denial of certain medications) may outweigh the benefits. These concerns were shared across groups but were more strongly expressed among participants with chronic mental health diagnoses. Conclusion: Clinical implementation of pharmacogenetic testing must address patient concerns about privacy, discrimination, quality of care, and erosion of the physician-patient relationship. PMID:26057686

  6. Pharmacogenetics in primary care: the promise of personalized medicine and the reality of racial profiling.

    PubMed

    Hunt, Linda M; Kreiner, Meta J

    2013-03-01

    Many anticipate that expanding knowledge of genetic variations associated with disease risk and medication response will revolutionize clinical medicine, making possible genetically based Personalized Medicine where health care can be tailored to individuals, based on their genome scans. Pharmacogenetics has received especially strong interest, with many pharmaceutical developers avidly working to identify genetic variations associated with individual differences in drug response. While clinical applications of emerging genetic knowledge are becoming increasingly available, genetic tests for drug selection are not as yet widely accessible, and many primary care clinicians are unprepared to interpret genetic information. We conducted interviews with 58 primary care clinicians, exploring how they integrate emerging pharmacogenetic concepts into their practices. We found that in their current practices, pharmacogenetic innovations have not led to individually tailored treatment, but instead have encouraged use of essentialized racial/ethnic identity as a proxy for genetic heritage. Current manifestations of Personalized Medicine appear to be reinforcing entrenched notions of inherent biological differences between racial groups, and promoting the belief that racial profiling in health care is supported by cutting-edge scientific authority. Our findings raise concern for how pharmacogenetic innovations will actually affect diverse populations, and how unbiased treatment can be assured.

  7. A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics

    PubMed Central

    Claudio-Campos, Karla; Rivera-Miranda, Giselle; Bermúdez-Bosch, Luis; Renta, Jessicca Y.; Cadilla, Carmen L.; Cruz, Iadelisse; Feliu, Juan F.; Vergara, Cunegundo; Ruaño, Gualberto

    2016-01-01

    Aim This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. Patients & Methods A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. Results The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). Conclusions Results supported our rationale to incorporate individual’s genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. Trial Registration ClinicalTrials.gov NCT01318057 PMID:26745506

  8. Social Network Analysis to Evaluate an Interdisciplinary Research Center

    ERIC Educational Resources Information Center

    Aboelela, Sally W.; Merrill, Jacqueline A.; Carley, Kathleen M.; Larson, Elaine

    2007-01-01

    We sought to examine the growth of an interdisciplinary center using social network analysis techniques. Specific aims were to examine the patterns of growth and interdisciplinary connectedness of the Center and to identify the social network characteristics of its productive members. The setting for this study was The Center for Interdisciplinary…

  9. Hierarchical Network Models for Education Research: Hierarchical Latent Space Models

    ERIC Educational Resources Information Center

    Sweet, Tracy M.; Thomas, Andrew C.; Junker, Brian W.

    2013-01-01

    Intervention studies in school systems are sometimes aimed not at changing curriculum or classroom technique, but rather at changing the way that teachers, teaching coaches, and administrators in schools work with one another--in short, changing the professional social networks of educators. Current methods of social network analysis are…

  10. The Georgia Psychoeducational Network (GPN) Research Report, 1989.

    ERIC Educational Resources Information Center

    Swan, William W., Ed.; Brown, Carvin L., Ed.

    1989-01-01

    This collection of papers includes five articles on the education of students with emotional and/or behavioral disorders participating in the Georgia Psychoeducational Network Program (GPN). "Training Needs of Fully Certified BD Teachers in the Georgia Psychoeducational Network" (Robert J. Stansberry) found, in a survey of 203 certified teachers…

  11. Participatory Research: An Emerging Alternative Methodology in Social Science Research. Participatory Research Network Series No. 2.

    ERIC Educational Resources Information Center

    Kassam, Yusuf, Ed.; Mustafa, Kemal, Ed.

    This book, consisting of a series of discussion papers and case studies, is a compilation of the papers presented at a region 1 workshop on participatory research in Africa. Included in the volume are the following discussion papers: "The Concept of Development in the Social Sciences," by Kemal Mustafa and Deborah Bryceson; "The Politics of…

  12. Some data-driven reflections on priorities in AIDS network research.

    PubMed

    Friedman, Samuel R; Bolyard, Melissa; Mateu-Gelabert, Pedro; Goltzman, Paula; Pawlowicz, Maria Pia; Singh, Dhan Zunino; Touze, Graciela; Rossi, Diana; Maslow, Carey; Sandoval, Milagros; Flom, Peter L

    2007-09-01

    Risk networks can transmit HIV or other infections; social networks can transmit social influence and thus help shape norms and behaviors. This primarily-theoretical paper starts with a review of network concepts, and then presents data from a New York network study to study patterns of sexual and injection linkages among IDUs and other drug users and nonusers, men who have sex with men, women who have sex with women, other men and other women in a high-risk community and the distribution of HIV, sex at group sex events, and health intravention behaviors in this network. It then discusses how risk network microstructures might influence HIV epidemics and urban vulnerability to epidemics; what social and other forces (such as "Big Events" like wars or ecological disasters) might shape networks and their associated norms, intraventions, practices and behaviors; and how network theory and research have and may continue to contribute to developing interventions against HIV epidemics. PMID:17053857

  13. Research on urban public traffic network with multi-weights based on single bus transfer junction

    NASA Astrophysics Data System (ADS)

    An, Xin-lei; Zhang, Li; Zhang, Jian-gang

    2015-10-01

    Regarding single bus transfer junction as a research object, this paper constructs the urban traffic network models with multi-weights taking different bus lines in bus transfer junction as the network nodes, that is, the urban traffic network with multi-weights is given different properties weights at every edge. According to the method of network split, the complex network with multi-weights is split into several different single weighted complex networks. Then, we study the global synchronization of the new network model by changing congestion degrees, transfers coefficient and passenger flow density between different bus lines. Finally, analytical and simulated results are given to show the impact of different properties weights to the public traffic network balance.

  14. Development of the Massachusetts School Nurse Research Network (MASNRN): A Practice-Based Research Network to Improve the Quality of School Nursing Practice

    ERIC Educational Resources Information Center

    Vessey, Judith A.

    2007-01-01

    When school nurses embrace evidence-based practice (EBP), higher-quality care is provided to students, their families, and the larger community. Despite this, school nursing has been slow to embrace EBP. Practice-Based Research Networks (PBRNs), which capitalize on the combined strengths of clinicians and researchers to study clinical questions,…

  15. Understanding Naltrexone Mechanism of Action and Pharmacogenetics in Asian Americans via Behavioral Economics: A Preliminary Study

    PubMed Central

    Bujarski, Spencer; MacKillop, James; Ray, Lara A.

    2013-01-01

    Rationale A behavioral economic approach to understanding the relative value of alcohol may be useful for advancing medication development for alcoholism. Naltrexone is a heavily researched and moderately effective treatment for alcohol dependence making it a good candidate for a proof-of-concept study of behavioral economics and alcoholism pharmacotherapy. Objectives This study examines naltrexone efficacy and pharmacogenetics in terms of the relative value of alcohol, assessed via demand curve analysis. Materials and Methods Participants were 35 heavy drinking (AUDIT ≥ 8) Asian Americans. A within-subjects cross-over medication design was used along with an intravenous alcohol challenge completed after four days of both naltrexone and placebo. At baseline and BrAC = 0.06 g/dl, participants completed an Alcohol Purchase Task, which assessed estimated alcohol consumption along escalating prices. Behavioral economic demand curve analysis yielded measures of Intensity, Elasticity, maximum expenditure (Omax), proportionate price insensitivity (Pmax) and breakpoint. Results Compared to placebo, naltrexone significantly reduced Intensity, Omax and breakpoint. There were also a trend level medication effects on Pmax. BrAC was associated with increases in Pmax and breakpoint. A significant naltrexone × OPRM1 genotype interaction was observed for intensity of demand. Conclusion The present study extends the literature on naltrexone’s mechanisms through the application of a novel behavioral economic paradigm. These results indicate that naltrexone reduces several indices of demand for alcohol. This preliminary report provides further evidence for the effectiveness of naltrexone and supports the utility of a behavioral economic approach to alcoholism pharmacotherapy development. PMID:22429255

  16. The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet)

    PubMed Central

    de Andrade, Joao; Schwarz, Marvin; Collard, Harold R.; Gentry-Bumpass, Tedryl; Colby, Thomas; Lynch, David; Schwarz, M.; Zisman, D. A.; Hunninghake, G.; Chapman, J.; Olman, M.; Lubell, S.; Morrison, L. D.; Steele, M. P.; Haram, T.; Roman, J.; Perez, R.; Perez, T.; Ryu, J. H.; Utz, J. P.; Limper, A. H.; Daniels, C. E.; Meiras, K.; Walsh, S.; Brown, K. K.; Schwarz, M.; Bair, C.; Kervitsky, D.; Lasky, J. A.; Ditta, S.; deAndrade, J.; Thannickal, V. J.; Stewart, M.; Zisman, D. A.; Lynch, J.; Calahan, E.; Lopez, P.; King, T. E.; Collard, H. R.; Golden, J. A.; Wolters, P. J.; Jeffrey, R.; Noth, I.; Hogarth, D. K.; Sandbo, N.; Strek, M. E.; White, S. R.; Brown, C.; Garic, I.; Maleckar, S.; Martinez, F. J.; Flaherty, K. R.; Han, M.; Moore, B.; Toews, G. B.; Dahlgren, D.; Raghu, G.; Hayes, J.; Snyder, M.; Loyd, J. E.; Lancaster, L.; Lawson, W.; Greer, R.; Mason, W.; Kaner, R. J.; Monroy, V.; Wang, M.; Lynch, D. A.; Colby, T.; Anstrom, K. J.; Becker, R. C.; Eisenstein, E. L.; MacIntyre, N. R.; Morrison, L. D; Rochon, J.; Steele, M. P.; Sundy, J. S.; Davidson-Ray, L.; Dignacco, P.; Edwards, R.; Anderson, R.; Beci, R.; Calvert, S.; Cain, K.; Gentry-Bumpass, T.; Hill, D.; Ingham, M.; Kagan, E.; Kaur, J.; Matti, C.; McClelland, J.; Meredith, A.; Nguyen, T.; Pesarchick, J.; Roberts, R. S.; Tate, W.; Thomas, T.; Walker, J.; Whelan, D.; Winsor, J.; Yang, Q.; Yow, E.; Reynolds, H. Y.; Tian, X.; Kiley, J.; Noth, I.; Olman, M.; Schwarz, M.; Toews, G. B.; Hunninghake, G.; Culver, D. A.; Chapman, J.; Olman, M.; Lubell, S.; Wehrmann, R.; Morrison, L. D.; Steele, M. P.; Haram, T.; Kidd, R.; Kallay, M.; Lyda, E.; Ryu, J. H.; Utz, J. P.; Limper, A. H.; Daniels, C. E.; Meiras, K.; Walsh, S.; Sahn, S.; O’Banner, N.; Stokes, F.; Brown, K. K.; Bair, C.; Kervitsky, D.; Ettinger, N. A.; Merli, S.; de Andrade, J.; Thannickal, V. J.; Stewart, M.; Belperio, J.; Lynch, J. P.; Calahan, E.; Lopez, P.; King, T. E.; Collard, H. R.; Golden, J.; Wolters, P.; Eller, A.; Noth, I.; Hogarth, D. K.; Sandbo, N.; Strek, M. E.; Maleckar, S.; Rahimova, G.; Sardin, L.; Roman, J.; Perez, R.; Perez, T.; Glassberg, M.; Simonet, E.; Martinez, F. J.; Baumann, K.; Chan, K.; Chughtai, A.; Gross, B.; Flaherty, K. R.; Han, M. L.; Hyzy, R.; Kazerooni, E.; Moore, B.; Myers, J.; Toews, G. B.; White, E.; Dahlgren, D.; Rossman, M.; Kreider, M.; Le, K.; Fitzgerald, J.; Glazer, C.; Scholand, M. B.; Brewster, L.; Johnson, A.; Raghu, G.; Berry-Bell, P.; Snydsman, A.; Loyd, J. E.; Lancaster, L.; Lawson, W.; Greer, R.; Kinser, K.; Richardson, R.; Mason, W.; Kaner, R. J.; Bandong, K.; Antin-Ozerkis, D.; Holm, C.; Estrom, J.; Lynch, D. A.; Colby, T.; Anstrom, K. J.; Eisenstein, E. L.; Sundy, J. S.; Davidson-Ray, L.; Dignacco, P.; Edwards, R.; Beci, R.; Calvert, S.; Gentry-Bumpass, T.; Hill, D.; Hofmann, P. V.; Hwang, K.; Kaur, J.; Matti, C.; Meredith, A.; Pesarchick, J.; Ramey, S.; Roberts, R. S.; Sharlow, A.; Winsor, J.; Yang, Q.; Yow, E.; Weinmann, G. G.; Reynolds, H.; Schmetter, B.; Tian, X.; Kiley, J.; Martinez, F. J.; Raghu, G.; Schwarz, M.; Toews, G. B.; Zibrak, J.; Demersky, A.; Vey, M.; Rosas, I. O.; Debrosse, P.; Culver, D. A.; Chapman, J.; Olman, M.; Lubell, S.; Wehrmann, R.; Morrison, L. D.; Steele, M. P.; Haram, T.; Kidd, R.; Kallay, M.; Lyda, E.; Ryu, J. H.; Utz, J. P.; Limper, A. H.; Daniels, C. E.; Meiras, K.; Walsh, S.; Sahn, S.; O’Banner, N.; Stokes, F.; Padilla, M.; Berhanu, G.; Brown, K. K.; Bair, C.; Kervitsky, D.; Ettinger, N. A.; Merli, S.; Criner, G. J.; Swift, I. Q.; Satti, A.; Cordova, F.; Patel, N.; West, K.; Jones, G.; Lasky, J. A.; Ditta, S.; de Andrade, J.; Thannickal, V. J.; Stewart, M.; Belperio, J.; Lynch, J. P.; Calahan, E.; Lopez, P.; King, T. E.; Collard, H. R.; Golden, J.; Wolters, P.; Eller, A.; Noth, I.; Hogarth, D. K.; Sandbo, N.; Strek, M. E.; Maleckar, S.; Rahimova, G.; Sardin, L.; Roman, J.; Perez, R.; Perez, T.; Glassberg, M.; Simonet, E.; Martinez, F. J.; Baumann, K.; Chan, K.; Chughtai, A.; Gross, B.; Flaherty, K. R.; Han, M. L.; Hyzy, R.; Kazerooni, E.; Moore, B.; Myers, J.; Toews, G. B.; White, E.; Dahlgren, D.; Rossman, M.; Kreider, M.; Le, K.; Fitzgerald, J.; Glazer, C.; Scholand, M. B.; Brewster, L.; Johnson, A.; Raghu, G.; Berry-Bell, P.; Snydsman, A.; Loyd, J. E.; Lancaster, L.; Lawson, W.; Greer, R.; Mason, W.; Kaner, R. J.; Bandong, K.; Antin-Ozerkis, D.; Holm, C.; Estrom, J.; Lynch, D. A.; Colby, T.; Anstrom, K. J.; Becker, R. C.; Eisenstein, E. L.; Sundy, J. S.; Davidson-Ray, L.; Dignacco, P.; Edwards, R.; Beci, R.; Calvert, S.; Cain, K.; Gentry-Bumpass, T.; Hill, D.; Huang, K.; Kaur, J.; Matti, C.; Meredith, A.; Pesarchick, J.; Ramey, S.; Roberts, R. S.; Sharlow, A.; Winsor, J.; Yow, E.; Weinmann, G. G.; Reynolds, H.; Schmetter, B.; Tian, X.; Kiley, J.

    2015-01-01

    BACKGROUND: The National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) provided a structured review of cases in which there was uncertainty or disagreement regarding diagnosis or clinical event classification. This article describes the diagnosis and adjudication processes. METHODS: The diagnostic process was based on review of clinical data and high-resolution CT scans with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. The AC used a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures. RESULTS: The IPFnet trials screened 1,015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. The AC reviewed 88 suspected acute exacerbations (AExs), 93 nonelective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators, as necessary clinical data were often not collected, particularly when subjects were evaluated outside of the primary study site. CONCLUSIONS: The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early because of safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AExs and hospitalizations as outcome measures. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00517933, NCT00650091, NCT00957242; URL: www.clinicaltrials.gov PMID

  17. Stillbirth Collaborative Research Network: design, methods and recruitment experience.

    PubMed

    Parker, Corette B; Hogue, Carol J R; Koch, Matthew A; Willinger, Marian; Reddy, Uma M; Thorsten, Vanessa R; Dudley, Donald J; Silver, Robert M; Coustan, Donald; Saade, George R; Conway, Deborah; Varner, Michael W; Stoll, Barbara; Pinar, Halit; Bukowski, Radek; Carpenter, Marshall; Goldenberg, Robert

    2011-09-01

    The Stillbirth Collaborative Research Network (SCRN) has conducted a multisite, population-based, case-control study, with prospective enrollment of stillbirths and livebirths at the time of delivery. This paper describes the general design, methods and recruitment experience. The SCRN attempted to enroll all stillbirths and a representative sample of livebirths occurring to residents of pre-defined geographical catchment areas delivering at 59 hospitals associated with five clinical sites. Livebirths <32 weeks gestation and women of African descent were oversampled. The recruitment hospitals were chosen to ensure access to at least 90% of all stillbirths and livebirths to residents of the catchment areas. Participants underwent a standardised protocol including maternal interview, medical record abstraction, placental pathology, biospecimen testing and, in stillbirths, post-mortem examination. Recruitment began in March 2006 and was completed in September 2008 with 663 women with a stillbirth and 1932 women with a livebirth enrolled, representing 69% and 63%, respectively, of the women identified. Additional surveillance for stillbirths continued until June 2009 and a follow-up of the case-control study participants was completed in December 2009. Among consenting women, there were high consent rates for the various study components. For the women with stillbirths, 95% agreed to a maternal interview, chart abstraction and a placental pathological examination; 91% of the women with a livebirth agreed to all of these components. Additionally, 84% of the women with stillbirths agreed to a fetal post-mortem examination. This comprehensive study is poised to systematically study a wide range of potential causes of, and risk factors for, stillbirths and to better understand the scope and incidence of the problem.

  18. Stillbirth Collaborative Research Network: Design, Methods and Recruitment Experience

    PubMed Central

    Parker, Corette B.; Hogue, Carol J. Rowland; Koch, Matthew A.; Willinger, Marian; Reddy, Uma; Thorsten, Vanessa R.; Dudley, Donald J.; Silver, Robert M.; Coustan, Donald; Saade, George R.; Conway, Deborah; Varner, Michael W.; Stoll, Barbara; Pinar, Halit; Bukowski, Radek; Carpenter, Marshall; Goldenberg, Robert

    2013-01-01

    SUMMARY The Stillbirth Collaborative Research Network (SCRN) has conducted a multisite, population-based, case-control study, with prospective enrollment of stillbirths and live births at the time of delivery. This paper describes the general design, methods, and recruitment experience. The SCRN attempted to enroll all stillbirths and a representative sample of live births occurring to residents of pre-defined geographic catchment areas delivering at 59 hospitals associated with five clinical sites. Live births <32 weeks gestation and women of African descent were oversampled. The recruitment hospitals were chosen to ensure access to at least 90% of all stillbirths and live births to residents of the catchment areas. Participants underwent a standardized protocol including maternal interview, medical record abstraction, placental pathology, biospecimen testing, and, in stillbirths, postmortem examination. Recruitment began in March 2006 and was completed in September 2008 with 663 women with a stillbirth and 1932 women with a live birth enrolled, representing 69% and 63%, respectively, of the women identified. Additional surveillance for stillbirth continued through June 2009 and a follow-up of the case-control study participants was completed in December 2009. Among consenting women, there were high consent rates for the various study components. For the women with stillbirth, 95% agreed to maternal interview, chart abstraction, and placental pathologic examination; 91% of the women with live birth agreed to all of these components. Additionally, 84% of the women with stillbirth agreed to a fetal postmortem examination. This comprehensive study is poised to systematically study a wide range of potential causes of, and risk factors for, stillbirth and to better understand the scope and incidence of the problem. PMID:21819424

  19. Is a practice-based rural research network feasible in Europe?

    PubMed

    Klemenc-Ketis, Zalika; Kurpas, Donata; Tsiligianni, Ioanna; Petrazzuoli, Ferdinando; Jacquet, Jean-Pierre; Buono, Nicola; Lopez-Abuin, Jose; Lionis, Christos

    2015-01-01

    Research in family medicine is a well-established entity nationally and internationally, covering all aspects of primary care including remote and isolated practices. However, due to limited capacity and resources in rural family medicine, its potential is not fully exploited yet. An idea to foster European rural primary care research by establishing a practice-based research network has been recently put forward by several members of the European Rural and Isolated Practitioners Association (EURIPA) and the European General Practice Research Network (EGPRN). Two workshops on why, and how to design a practice-based research network among rural family practices in Europe were conducted at two international meetings. This paper revisits the definition of practice-based research in family medicine, reflects on the current situation in Europe regarding the research in rural family practice, and discusses a rationale for practice-based research in rural family medicine. A SWOT analysis was used as the main tool to analyse the current situation in Europe regarding the research in rural family practice at both meetings. The key messages gained from these meetings may be employed by the Wonca Working Party on research, the International Federation of Primary Care Research Network and the EGPRN that seek to introduce a practice-based research approach. The cooperation and collaboration between EURIPA and EGPRN creates a fertile ground to discuss further the prospect of a European practice-based rural family medicine research network, and to draw on the joint experience. PMID:26134091

  20. Is a practice-based rural research network feasible in Europe?

    PubMed

    Klemenc-Ketis, Zalika; Kurpas, Donata; Tsiligianni, Ioanna; Petrazzuoli, Ferdinando; Jacquet, Jean-Pierre; Buono, Nicola; Lopez-Abuin, Jose; Lionis, Christos

    2015-01-01

    Research in family medicine is a well-established entity nationally and internationally, covering all aspects of primary care including remote and isolated practices. However, due to limited capacity and resources in rural family medicine, its potential is not fully exploited yet. An idea to foster European rural primary care research by establishing a practice-based research network has been recently put forward by several members of the European Rural and Isolated Practitioners Association (EURIPA) and the European General Practice Research Network (EGPRN). Two workshops on why, and how to design a practice-based research network among rural family practices in Europe were conducted at two international meetings. This paper revisits the definition of practice-based research in family medicine, reflects on the current situation in Europe regarding the research in rural family practice, and discusses a rationale for practice-based research in rural family medicine. A SWOT analysis was used as the main tool to analyse the current situation in Europe regarding the research in rural family practice at both meetings. The key messages gained from these meetings may be employed by the Wonca Working Party on research, the International Federation of Primary Care Research Network and the EGPRN that seek to introduce a practice-based research approach. The cooperation and collaboration between EURIPA and EGPRN creates a fertile ground to discuss further the prospect of a European practice-based rural family medicine research network, and to draw on the joint experience.

  1. Architecture of the Multi-Modal Organizational Research and Production Heterogeneous Network (MORPHnet)

    SciTech Connect

    Aiken, R.J.; Carlson, R.A.; Foster, I.T.

    1997-01-01

    The research and education (R&E) community requires persistent and scaleable network infrastructure to concurrently support production and research applications as well as network research. In the past, the R&E community has relied on supporting parallel network and end-node infrastructures, which can be very expensive and inefficient for network service managers and application programmers. The grand challenge in networking is to provide support for multiple, concurrent, multi-layer views of the network for the applications and the network researchers, and to satisfy the sometimes conflicting requirements of both while ensuring one type of traffic does not adversely affect the other. Internet and telecommunications service providers will also benefit from a multi-modal infrastructure, which can provide smoother transitions to new technologies and allow for testing of these technologies with real user traffic while they are still in the pre-production mode. The authors proposed approach requires the use of as much of the same network and end system infrastructure as possible to reduce the costs needed to support both classes of activities (i.e., production and research). Breaking the infrastructure into segments and objects (e.g., routers, switches, multiplexors, circuits, paths, etc.) gives the capability to dynamically construct and configure the virtual active networks to address these requirements. These capabilities must be supported at the campus, regional, and wide-area network levels to allow for collaboration by geographically dispersed groups. The Multi-Modal Organizational Research and Production Heterogeneous Network (MORPHnet) described in this report is an initial architecture and framework designed to identify and support the capabilities needed for the proposed combined infrastructure and to address related research issues.

  2. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    PubMed

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

  3. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    PubMed

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network.

  4. Visualizing and Evaluating the Growth of Multi-Institutional Collaboration Based on Research Network Analysis

    PubMed Central

    Luo, Jake; Pelfrey, Clara; Zhang, Guo-Qiang

    2014-01-01

    Research collaboration plays an important role in scientific productivity and academic innovation. Multi-institutional collaboration has become a vital approach for integrating multidisciplinary resources and expertise to enhance biomedical research. There is an increasing need for analyzing the effect of multi-institutional research collaboration. In this paper, we present a collaboration analysis pipeline based on research networks constructed from publication co-authorship relationship. Such research networks can be effectively used to render and analyze large-scale institutional collaboration. The co-authorship networks of the Cleveland Clinical and Translational Science Collaborative (CTSC) were visualized and analyzed. SciVal Expert™ was used to extract publication data of the CTSC members. The network was presented in informative and aesthetically appealing diagrams using the open source visualization package Gephi. The analytic result demonstrates the effectiveness of our approach, and it also indicates the substantial growth of research collaboration among the CTSC members crossing its partner institutions. PMID:25954579

  5. Visualizing and evaluating the growth of multi-institutional collaboration based on research network analysis.

    PubMed

    Luo, Jake; Pelfrey, Clara; Zhang, Guo-Qiang

    2014-01-01

    Research collaboration plays an important role in scientific productivity and academic innovation. Multi-institutional collaboration has become a vital approach for integrating multidisciplinary resources and expertise to enhance biomedical research. There is an increasing need for analyzing the effect of multi-institutional research collaboration. In this paper, we present a collaboration analysis pipeline based on research networks constructed from publication co-authorship relationship. Such research networks can be effectively used to render and analyze large-scale institutional collaboration. The co-authorship networks of the Cleveland Clinical and Translational Science Collaborative (CTSC) were visualized and analyzed. SciVal Expert™ was used to extract publication data of the CTSC members. The network was presented in informative and aesthetically appealing diagrams using the open source visualization package Gephi. The analytic result demonstrates the effectiveness of our approach, and it also indicates the substantial growth of research collaboration among the CTSC members crossing its partner institutions.

  6. Dynamics of Social Complex Networks: Some Insights into Recent Research

    NASA Astrophysics Data System (ADS)

    Lozano, Sergi

    Social networks analysis (that is, the study of interactions among social actors from a structural viewpoint) has a long tradition covering several decades [1, 2, 3]. This sort of study has usually been performed over small social networks, and the limitation of size has conditioned the visibility of complexity [4, 5]. However, the situation has changed significantly in recent times due to basically two reasons. First, there is an increasing availability of larger social datasets (obtained in most cases from information and communication technologies). Secondly, a large number of physicists and other scholars from complexity science have started to take active interest in the field. New perspectives and tools have been provided by these ‘newcomers’, which in combination with the expertise and knowledge accumulated by ‘classical’ social network analysts, has formed the basis of a multidisciplinary field suitably termed the science of networks [6, 7].

  7. Microfabrication of cylindrical microfluidic channel networks for microvascular research.

    PubMed

    Huang, Zhouchun; Li, Xiang; Martins-Green, Manuela; Liu, Yuxin

    2012-10-01

    Current methods for formation of microvascular channel scaffolds are limited with non-circular channel cross-sections, complicated fabrication, and less flexibility in microchannel network design. To address current limitations in the creation of engineered microvascular channels with complex three-dimensional (3-D) geometries in the shape of microvessels, we have developed a reproducible, cost-effective, and flexible micromanufacturing process combined with photolithographic reflowable photoresist and soft lithography techniques to fabricate cylindrical microchannel and networks. A positive reflowable photoresist AZ P4620 was used to fabricate a master microchannel mold with semi-circular cross-sections. By the alignment and bonding of two polydimethylsiloxane (PDMS) microchannels replicated from the master mold together, a cylindrical microchannel or microchannel network was created. Further examination of the channel dimensions and surface profiles at different branching levels showed that the shape of the microfluidic channel was well approximated by a semi-circular surface, and a multi-level, multi-depth channel network was created. In addition, a computational fluidic dynamics (CFD) model was used to simulate shear flows and corresponding pressure distributions inside of the microchannel and channel network based on the dimensions of the fabricated channels. The fabricated multi-depth cylindrical microchannel network can provide platforms for the investigation of microvascular cells growing inside of cylindrical channels under shear flows and lumen pressures, and work as scaffolds for the investigation of morphogenesis and tubulogenesis. PMID:22729782

  8. Microfabrication of cylindrical microfluidic channel networks for microvascular research.

    PubMed

    Huang, Zhouchun; Li, Xiang; Martins-Green, Manuela; Liu, Yuxin

    2012-10-01

    Current methods for formation of microvascular channel scaffolds are limited with non-circular channel cross-sections, complicated fabrication, and less flexibility in microchannel network design. To address current limitations in the creation of engineered microvascular channels with complex three-dimensional (3-D) geometries in the shape of microvessels, we have developed a reproducible, cost-effective, and flexible micromanufacturing process combined with photolithographic reflowable photoresist and soft lithography techniques to fabricate cylindrical microchannel and networks. A positive reflowable photoresist AZ P4620 was used to fabricate a master microchannel mold with semi-circular cross-sections. By the alignment and bonding of two polydimethylsiloxane (PDMS) microchannels replicated from the master mold together, a cylindrical microchannel or microchannel network was created. Further examination of the channel dimensions and surface profiles at different branching levels showed that the shape of the microfluidic channel was well approximated by a semi-circular surface, and a multi-level, multi-depth channel network was created. In addition, a computational fluidic dynamics (CFD) model was used to simulate shear flows and corresponding pressure distributions inside of the microchannel and channel network based on the dimensions of the fabricated channels. The fabricated multi-depth cylindrical microchannel network can provide platforms for the investigation of microvascular cells growing inside of cylindrical channels under shear flows and lumen pressures, and work as scaffolds for the investigation of morphogenesis and tubulogenesis.

  9. winderosionnetwork.org - Portal to the National Wind Erosion Research Network

    NASA Astrophysics Data System (ADS)

    Webb, N.; Herrick, J. E.; Clingan, S.; Cooper, B.; Courtright, E.; LaPlante, V.; Van Zee, J.

    2015-12-01

    The National Wind Erosion Research Network was established in 2014 as a collaborative effort led by the USDA Agricultural Research Service and Natural Resources Conservation Service, and USDI Bureau of Land Management, to address the need for standardized measurements of wind erosion and its controlling factors. Data will be used to support model development and identification of improved land management strategies that have global applications. By applying standard methods, the Network will overcome the common challenge of synthesizing independent studies to assess local-to-national scale wind erosion and dust emission. Twelve intensively instrumented Network sites will be operational by spring 2016, providing high-resolution measurements of aeolian sediment transport rates, meteorological conditions and soil and vegetation properties. These initial sites are located across rangelands and croplands in New Mexico, Texas, Arizona, California, Nevada, Colorado, Utah, North Dakota, Idaho and Washington. A primary objective of the Network is to facilitate collaboration among Network sites and the wider research community to address basic research questions about aeolian processes, model development, and evaluate practical management options. In support of Network activities, winderosionnetwork.org was developed to serve as a Network data portal, and provide online information about the National Wind Erosion Research Network including protocols and results. The website provides a comprehensive resource for scientists and managers interested in engaging with the Network and accessing Network products. The Network provides exciting opportunities to engage in a national long-term wind erosion research program that promises significant impact for our understanding and ability to predict and evaluate aeolian processes across land cover types and land use systems.

  10. 'The Tsukuba Network' as a new medium for promoting research communications in Tsukuba

    NASA Astrophysics Data System (ADS)

    Taguchi, Masamichi

    The Science and Technology Agency constructed a PC-based communication network system named 'The Tsukuba Network' as a new medium for promoting the research communication in, and with, the Tsukuba City. For about a year prior to full operation, a pilot system was operated with the cooperation of some monitoring users to gain skill and experience for managing the PC-based communication network. The main service functions of the system are : bulletin board service; electronic mail ; construction of, and access to, the databases involving research information in Tsukuba City ; electronic conference; common use of softwares ; connection to other communication networks ( e.g., university and local network). The host computer is a work station EWS4800 and the network processor is a personal computer PC-9801 . These two computers are connected with LAN.

  11. Undergraduate students' development of social, cultural, and human capital in a networked research experience

    NASA Astrophysics Data System (ADS)

    Thompson, Jennifer Jo; Conaway, Evan; Dolan, Erin L.

    2015-04-01

    Recent calls for reform in undergraduate biology education have emphasized integrating research experiences into the learning experiences of all undergraduates. Contemporary science research increasingly demands collaboration across disciplines and institutions to investigate complex research questions, providing new contexts and models for involving undergraduates in research. In this study, we examined the experiences of undergraduates participating in a multi-institution and interdisciplinary biology research network. Unlike the traditional apprenticeship model of research, in which a student participates in research under the guidance of a single faculty member, students participating in networked research have the opportunity to develop relationships with additional faculty and students working in other areas of the project, at their own and at other institutions. We examined how students in this network develop social ties and to what extent a networked research experience affords opportunities for students to develop social, cultural, and human capital. Most studies of undergraduate involvement in science research have focused on documenting student outcomes rather than elucidating how students gain access to research experiences or how elements of research participation lead to desired student outcomes. By taking a qualitative approach framed by capital theories, we have identified ways that undergraduates utilize and further develop various forms of capital important for success in science research. In our study of the first 16 months of a biology research network, we found that undergraduates drew upon a combination of human, cultural, and social capital to gain access to the network. Within their immediate research groups, students built multidimensional social ties with faculty, peers, and others, yielding social capital that can be drawn upon for information, resources, and support. They reported developing cultural capital in the form of learning to

  12. Brain extracellular matrix meets COST--matrix for European research networks.

    PubMed

    Gajović, Srećko; Pochet, Roland

    2014-01-01

    Today's researchers are faced with a change from curiosity-driven to mandate-driven research. These two approaches are well combined within scientific networks (Actions) supported by the European Cooperation in Science and Technology (COST) program. The functioning of COST Actions, although directed only to networking, has a substantial impact on European science and can be compared to the functioning of the extracellular matrix in the brain, which although scarce plays a key role in initiation, maintenance, and plasticity of intercellular interactions in the nervous system. COST networks enable interdisciplinary approach and support early-stage researchers, which is a vital asset for the advancement of science. PMID:25410370

  13. pSCANNER: patient-centered Scalable National Network for Effectiveness Research.

    PubMed

    Ohno-Machado, Lucila; Agha, Zia; Bell, Douglas S; Dahm, Lisa; Day, Michele E; Doctor, Jason N; Gabriel, Davera; Kahlon, Maninder K; Kim, Katherine K; Hogarth, Michael; Matheny, Michael E; Meeker, Daniella; Nebeker, Jonathan R

    2014-01-01

    This article describes the patient-centered Scalable National Network for Effectiveness Research (pSCANNER), which is part of the recently formed PCORnet, a national network composed of learning healthcare systems and patient-powered research networks funded by the Patient Centered Outcomes Research Institute (PCORI). It is designed to be a stakeholder-governed federated network that uses a distributed architecture to integrate data from three existing networks covering over 21 million patients in all 50 states: (1) VA Informatics and Computing Infrastructure (VINCI), with data from Veteran Health Administration's 151 inpatient and 909 ambulatory care and community-based outpatient clinics; (2) the University of California Research exchange (UC-ReX) network, with data from UC Davis, Irvine, Los Angeles, San Francisco, and San Diego; and (3) SCANNER, a consortium of UCSD, Tennessee VA, and three federally qualified health systems in the Los Angeles area supplemented with claims and health information exchange data, led by the University of Southern California. Initial use cases will focus on three conditions: (1) congestive heart failure; (2) Kawasaki disease; (3) obesity. Stakeholders, such as patients, clinicians, and health service researchers, will be engaged to prioritize research questions to be answered through the network. We will use a privacy-preserving distributed computation model with synchronous and asynchronous modes. The distributed system will be based on a common data model that allows the construction and evaluation of distributed multivariate models for a variety of statistical analyses.

  14. pSCANNER: patient-centered Scalable National Network for Effectiveness Research

    PubMed Central

    Ohno-Machado, Lucila; Agha, Zia; Bell, Douglas S; Dahm, Lisa; Day, Michele E; Doctor, Jason N; Gabriel, Davera; Kahlon, Maninder K; Kim, Katherine K; Hogarth, Michael; Matheny, Michael E; Meeker, Daniella; Nebeker, Jonathan R

    2014-01-01

    This article describes the patient-centered Scalable National Network for Effectiveness Research (pSCANNER), which is part of the recently formed PCORnet, a national network composed of learning healthcare systems and patient-powered research networks funded by the Patient Centered Outcomes Research Institute (PCORI). It is designed to be a stakeholder-governed federated network that uses a distributed architecture to integrate data from three existing networks covering over 21 million patients in all 50 states: (1) VA Informatics and Computing Infrastructure (VINCI), with data from Veteran Health Administration's 151 inpatient and 909 ambulatory care and community-based outpatient clinics; (2) the University of California Research exchange (UC-ReX) network, with data from UC Davis, Irvine, Los Angeles, San Francisco, and San Diego; and (3) SCANNER, a consortium of UCSD, Tennessee VA, and three federally qualified health systems in the Los Angeles area supplemented with claims and health information exchange data, led by the University of Southern California. Initial use cases will focus on three conditions: (1) congestive heart failure; (2) Kawasaki disease; (3) obesity. Stakeholders, such as patients, clinicians, and health service researchers, will be engaged to prioritize research questions to be answered through the network. We will use a privacy-preserving distributed computation model with synchronous and asynchronous modes. The distributed system will be based on a common data model that allows the construction and evaluation of distributed multivariate models for a variety of statistical analyses. PMID:24780722

  15. Cyber Security Research Frameworks For Coevolutionary Network Defense

    SciTech Connect

    Rush, George D.; Tauritz, Daniel Remy

    2015-12-03

    Several architectures have been created for developing and testing systems used in network security, but most are meant to provide a platform for running cyber security experiments as opposed to automating experiment processes. In the first paper, we propose a framework termed Distributed Cyber Security Automation Framework for Experiments (DCAFE) that enables experiment automation and control in a distributed environment. Predictive analysis of adversaries is another thorny issue in cyber security. Game theory can be used to mathematically analyze adversary models, but its scalability limitations restrict its use. Computational game theory allows us to scale classical game theory to larger, more complex systems. In the second paper, we propose a framework termed Coevolutionary Agent-based Network Defense Lightweight Event System (CANDLES) that can coevolve attacker and defender agent strategies and capabilities and evaluate potential solutions with a custom network defense simulation. The third paper is a continuation of the CANDLES project in which we rewrote key parts of the framework. Attackers and defenders have been redesigned to evolve pure strategy, and a new network security simulation is devised which specifies network architecture and adds a temporal aspect. We also add a hill climber algorithm to evaluate the search space and justify the use of a coevolutionary algorithm.

  16. [Analysis of researchers' implication in a research-intervention in the Stork Network: a tool for institutional analysis].

    PubMed

    Fortuna, Cinira Magali; Mesquita, Luana Pinho de; Matumoto, Silvia; Monceau, Gilles

    2016-01-01

    This qualitative study is based on institutional analysis as the methodological theoretical reference with the objective of analyzing researchers' implication during a research-intervention and the interferences caused by this analysis. The study involved researchers from courses in medicine, nursing, and dentistry at two universities and workers from a Regional Health Department in follow-up on the implementation of the Stork Network in São Paulo State, Brazil. The researchers worked together in the intervention and in analysis workshops, supported by an external institutional analysis. Two institutions stood out in the analysis: the research, established mainly with characteristics of neutrality, and management, with Taylorist characteristics. Differences between researchers and difficulties in identifying actions proper to network management and research were some of the interferences that were identified. The study concludes that implication analysis is a powerful tool for such studies. PMID:27653198

  17. Networks of Collaboration among Scientists in a Center for Diabetes Translation Research

    PubMed Central

    Harris, Jenine K.; Wong, Roger; Thompson, Kellie; Haire-Joshu, Debra; Hipp, J. Aaron

    2015-01-01

    Background Transdisciplinary collaboration is essential in addressing the translation gap between scientific discovery and delivery of evidence-based interventions to prevent and treat diabetes. We examined patterns of collaboration among scientists at the Washington University Center for Diabetes Translation Research. Methods Members (n = 56) of the Washington University Center for Diabetes Translation Research were surveyed about collaboration overall and on publications, presentations, and grants; 87.5% responded (n = 49). We used traditional and network descriptive statistics and visualization to examine the networks and exponential random graph modeling to identify predictors of collaboration. Results The 56 network members represented nine disciplines. On average, network members had been affiliated with the center for 3.86 years (s.d. = 1.41). The director was by far the most central in all networks. The overall and publication networks were the densest, while the overall and grant networks were the most centralized. The grant network was the most transdisciplinary. The presentation network was the least dense, least centralized, and least transdisciplinary. For every year of center affiliation, network members were 10% more likely to collaborate (OR: 1.10; 95% CI: 1.00–1.21) and 13% more likely to write a paper together (OR: 1.13; 95% CI: 1.02–1.25). Network members in the same discipline were over twice as likely to collaborate in the overall network (OR: 2.10; 95% CI: 1.40–3.15); however, discipline was not associated with collaboration in the other networks. Rank was not associated with collaboration in any network. Conclusions As transdisciplinary centers become more common, it is important to identify structural features, such as a central leader and ongoing collaboration over time, associated with scholarly productivity and, ultimately, with advancing science and practice. PMID:26301873

  18. Evaluating Research and Impact: A Bibliometric Analysis of Research by the NIH/NIAID HIV/AIDS Clinical Trials Networks

    PubMed Central

    Rosas, Scott R.; Kagan, Jonathan M.; Schouten, Jeffrey T.; Slack, Perry A.; Trochim, William M. K.

    2011-01-01

    Evaluative bibliometrics uses advanced techniques to assess the impact of scholarly work in the context of other scientific work and usually compares the relative scientific contributions of research groups or institutions. Using publications from the National Institute of Allergy and Infectious Diseases (NIAID) HIV/AIDS extramural clinical trials networks, we assessed the presence, performance, and impact of papers published in 2006–2008. Through this approach, we sought to expand traditional bibliometric analyses beyond citation counts to include normative comparisons across journals and fields, visualization of co-authorship across the networks, and assess the inclusion of publications in reviews and syntheses. Specifically, we examined the research output of the networks in terms of the a) presence of papers in the scientific journal hierarchy ranked on the basis of journal influence measures, b) performance of publications on traditional bibliometric measures, and c) impact of publications in comparisons with similar publications worldwide, adjusted for journals and fields. We also examined collaboration and interdisciplinarity across the initiative, through network analysis and modeling of co-authorship patterns. Finally, we explored the uptake of network produced publications in research reviews and syntheses. Overall, the results suggest the networks are producing highly recognized work, engaging in extensive interdisciplinary collaborations, and having an impact across several areas of HIV-related science. The strengths and limitations of the approach for evaluation and monitoring research initiatives are discussed. PMID:21394198

  19. Development of a Pharmacogenetic Predictive Test in asthma: proof of concept

    PubMed Central

    Wu, Ann Chen; Himes, Blanca E.; Lasky-Su, Jessica; Litonjua, Augusto; Li, Lingling; Lange, Christoph; Lima, John; Irvin, Charles G.; Weiss, Scott T.

    2013-01-01

    Objective To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). Methods We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 μg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. Results The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n= 422) and 0.60 (n= 475) and 0.63 (n= 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. Conclusion Our finding that genetic polymorphisms with a clinical trait are

  20. Research into alternative network approaches for space operations

    NASA Technical Reports Server (NTRS)

    Kusmanoff, Antone L.; Barton, Timothy J.

    1990-01-01

    The main goal is to resolve the interoperability problem of applications employing DOD TCP/IP (Department of Defence Transmission Control Protocol/Internet Protocol) family of protocols on a CCITT/ISO based network. The objective is to allow them to communicate over the CCITT/ISO protocol GPLAN (General Purpose Local Area Network) network without modification to the user's application programs. There were two primary assumptions associated with the solution that was actually realized. The first is that the solution had to allow for future movement to the exclusive use of the CCITT/ISO standards. The second is that the solution had to be software transparent to the currently installed TCP/IP and CCITT/ISO user application programs.